Stanford Antiviral Chronic Fatigue Syndrome Trial Promises Hope, But More Study Needed

November 21, 2012

by Cort Johnson

Before XMRV was Kogelnik/Montoya…the 2006 unblinded Kogelnik/Montoya study, finding that 6 months of Valcyte use returned 75% of participants to full health, hit the community like a lightning bolt. Yes, the study was very small (12 people) and it was unblinded, but the stories of recovery were so dramatic that it was hard to imagine they hadn’t hit gold. All that was left, it seemed, was to document the progress with a more rigorous, placebo-controlled study that appeared to be under way.

“These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.” (Kogelnik et al, 2006)

Six years later that study has still not shown up. This latest study by Montoya, which did not involve controls, is simply a retrospective analysis which examined the effect of Valganciclovir treatment on 61 patients treated at the Stanford clinic from 2004-2009 using a chart analysis.

Heavily ‘infected’ patients….

All patients had above normal HHV6 (>1:320), EBV VCA (1:640), EBV VCA (1:640) and EBV EA (1:160) IgG titers. The early EBV antibodies (EBV NA IGG), that Dr. Lerner and others believe are tied to aborted but simmering infections in ME/CFS, were also measured. Note that because healthy people can have similarly high titers, none of these titers are considered diagnostic of an active infection by most practitioners in the medical community.

Montoya has proposed, however, that high titers in the presence of certain symptoms are suggestive of an active infection. The authors noted that, while high titers can be found in healthy people, most healthy people have quite low herpesvirus titers while higher titers are commonly found in people with chronic fatigue syndrome. Something must be pushing those herpesvirus antibody titers higher in ME/CFS and, of course, an active herpesvirus infection is the first thing that comes to mind.

A patient was deemed a responder if self reports of cognitive and physical functioning increased by 30% or more at some point in treatment. The average patient age was 47 and the average length of illness was a hearty 10 years. The average treatment period was about 6 months – much shorter than recommended by Dr. Lerner.

Results

Almost 60% of patients responded physically and fully 80% responded cognitively – a nice response. As a group, patients rose from an average of 34/100 to 53/100 physically (56% jump) and from 43/100 to 66/100 cognitively (50% jump). (Unfortunately from the way the study was written the percentage increase could have been interpreted as 19% and 23%. Thanks to Tom Kindlon for pointing this out). Put another way, the patients jumped from being a third of normal physically to about half normal and from about 40% of normal cognitively to two-thirds normal.

This was blunted to some extent by the fact that only the highest data point, not an average, was used to assess effects. That means we know that, at least at one point in their treatment, 80% of the participants reported that they were at least 50% better cognitively, and almost 60% were improved physically by at least 50%, but we don’t know how long the effect lasted.

Teasing out the responders indicated that they improved an average of 34 and 37% respectively.

A look at the charts included in the paper indicated that there were some dramatic improvements. A couple of people went from a score of about 20-30 to 80-100 on physical functioning -meaning they were effectively well. Several others experienced dramatic improvements going from 0-20 to 50-60. (Two unfortunate people went from around 20 to less than 10). It was fairly easy to find 30-40 point gains – which equate to major improvements in functionality – but many people made smaller gains.

The most significant result may have been the quite strong finding (P<.0002) that longer treatment durations (7.4 months on average) resulted in improved benefits relative to shorter treatment durations (5.5 months). Long antiviral treatment regimes are a key feature of Dr. Lerner’s antiviral treatment protocol.

The authors called the findings ‘clinically striking’ when placed in context of how difficult it was to treat ME/CFS, and indeed most doctors would probably be very happy to see responses like this in their patients. (Their patients would be happy as well :))

Antibodies Strike Out

The antibody results indicated how much researchers still have to learn. The researchers thought that higher antibodies would be indicative of poorer health, but they were not, and antibody levels did not drop significantly more in the responders than in the non-responders. (There was a ‘trend’ toward better response in patients with high baseline antibodies). Whatever the effects of the trial, it did not appear to happen at the antibody level.

Potentially obscuring the antibody results, however, was the possibility that some patients may have hypogammaglobulemia (low B-cell and antibody levels), while others may have overly strong antibody responses, and bigger studies would be needed to tease out these factors. It’s possible that too many complicating factors were present for a finding of statistical significance to show up in a study of this size.

Figuring out why some people improve during antiviral treatment while others do not has been a key goal for Montoya, and he’s reportedly been plowing through immune findings to see if he can pick up measurements that change significantly as people get well. Finding that would give him and the ME/CFS research community a strong biomarker to concentrate on. (Dr. Kogelnik is looking at patients for this as well). This was not that study, however, and hopefully that paper will appear in the future.

Conclusion

Valcyte has not gone the way of XMRV. As with XMRV, the promise of an early study – in this case the 2006 unblinded one with its remarkable success rate – did not hold up, but this study was positive and many patients did improve – in many cases, it appears, significantly.

The study, though, was underpowered in many ways; it was retrospective, it was not placebo-controlled, and patients’ self-reports were rudimentary to say the least – they appear to have simply rated themselves on a scale from 0-100 on their physical and cognitive functioning and only the highest scores were used. The most intriguing result was the increased likelihood of benefit in patients with longer treatment duration – a key facet of Dr. Lerner’s program.

Without a blinded control group, however, all the results can be challenged – it can be argued that the responders were simply due to placebo, the benefit was transient, and the increased benefit with duration was simply an indicator that time in combination with placebo really does heal somewhat with ME/CFS.

The road to understanding the role that pathogens play in ME/CFS has been long and crooked. With all the interest in antivirals, it’s remarkable that we still do not have a single well-designed, rigorously controlled ME/CFS antiviral treatment trial. Every study, from Dr. Lerner’s trials to Dr. Montoya’s two studies, has had enough design flaws for skeptics to be able to discount the findings. There’s still a great deal of work to be done to figure out how and why antivirals are working when they do work in this disorder.

One such study was underway. In Dec 2010 we were informed that two papers from Dr. Montoya’s placebo-controlled, doubled blinded study – which involved extensive immune testing, exercise testing, etc – were in process. (We were also informed that the study we’ve just looked at would be published ‘soon’ :)). At a conference that year, Dr. Montoya reported that he was on the track of several immune biomarkers (IL-5, IL17F, ENA78, EOTAXN, IP10) that improved during treatment. He also reported that an early antigen marker usually associated with cancer may be a biomarker for this group.

The big EBV/HHV6 study is still to come…

46 comments

{ 46 comments… read them below or add one }

heapsreal November 21, 2012 at 8:01 pm

it would be interesting to see a study where they also test nk and cd8 function in those patients as well as compare antivirals with combo of antiviral and immune mod with a placebo treatment and seeing the before and after results of viral titres , nk and cd8 function. Im suprised further sudies havent been done but then alot also depends on drug companies and patents for new indications etc.

cheers!!!

Dolphin November 21, 2012 at 9:25 pm

Thanks Cort.
Small correction: Physical functioning changed from 34 (on a 100 point scale) to 53 (**not 56**) (on a 100 point scale), although it was a 56% improvement.

Mark November 21, 2012 at 11:57 pm
Dolphin

Thanks Cort.
Small correction: Physical functioning changed from 34 (on a 100 point scale) to 53 (**not 56**) (on a 100 point scale), although it was a 56% improvement.

Thanks Dolphin – I've fixed that now.

Waverunner November 22, 2012 at 2:24 am

Does anyone know when the placebo controlled study will be published? The improvement of bio-markers alone will not be sufficient enough to make clear statements about treatment success.

Snow Leopard November 22, 2012 at 3:09 am

Given that there was no significant difference in serology between responders and non-responders, (either baseline or changes), it seems to me that any improvement,must have been due to other factors, perhaps due to other immune system changes as a result of reducing the level of infection, or side effects of the drug itself.

Sasha November 22, 2012 at 3:16 am
Waverunner

Does anyone know when the placebo controlled study will be published? The improvement of bio-markers alone will not be sufficient enough to make clear statements about treatment success.

Yes, I'd like to know this too. Cort, are you in contact with Dr Montoya? Can you ask him?

Simon November 22, 2012 at 12:59 pm

Thanks for another great piece, Cort: its thorough, fair and a little depressing.

It's extraordinary that six years after a highly promising finding we still don't have a decent placebo-controlled study to properly evaluate the treatment.

There is a separate thread on this study, including some excellent analysis by Dolphin. This highlights issues raised by the study itself that they used peak scores – which may have come a long time after treatment was discontinued, suggesting the treatment may not be related to the improvement. Worse, the use of peak scores means that any patients with fluctuating scores will appear to improve since the highest peak will be recorded, while troughs will be ignored.

Montoya['s] reportedly been plowing through immune findings to see if he can pick up measurements that change significantly as people get well

That sounds alarmingly like data mining: your main hypothesis (high antibody titres) flops so you search through data for until you find an association that looks significant. Except if you search through enough possibilities, you'll find several 'significant' associations just by chance. Surely, after so many years working on this, if there was a genuine strong association then Montoya would have already found it?

Maybe one of Montoya's oft-promised studies will finally materialise and lift my gloom.

joshualevy November 23, 2012 at 12:30 pm

Cort, I think you are making a mistake when you say:

The most significant result may have been the quite strong finding (P<.0002) that longer treatment durations (7.4 months on average) resulted in improved benefits relative to shorter treatment durations (5.5 months). Long antiviral treatment regimes are a key feature of Dr. Lerner's antiviral treatment protocol.

Here are two possible source for this "longer treatment means bigger improvements" result:

Trough vs Peak differences will get bigger (on average) for longer study duration, if you are reporting only on peak results. This result could easily be a direct effect of the reporting design, where only peak results are reported. Basically, the longer duration gives more time for a randomly higher peak to be seen and reported.

Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news.

Other random points:
I think it's pretty clear that this research has failed, or is in deep-deep trouble.
Why? Because successful research moves forward. If a researcher does a successful intervention study with 12 people and no placebo, then the next experiment will be an intervention study with more than 12 people and/or a placebo group, and almost certainly both.

This research program took several steps backward. First: The earlier study was intervention, and the later study was population based, that's a HUGE step backward. Second: While it is ok for the first study is a research program to be no-placebo, once you have good results from that, the follow on studies should have a control group of some kind.

Also, using "peak scores" results for a disease like ME/CFS where patients are known to go through better and worse phases, is a major design flaw. It completely negates any results (my opinion, of course). What possible motivation could there be for a design like that, in a disease like this?

Remember, the drug Drs. Kogelnik and Montoya are testing is produced by some Pharma company. That company would love to sell it to millions of ME/CFS sufferers. So there should be plenty of money available to fund a follow-on study to expand the use of a drug. So whatever the problem, it's not a lack of funding.

Joshua (not Jay) Levy

Enid November 23, 2012 at 12:34 pm

Thanks Cort.

satoshikasumi November 23, 2012 at 9:32 pm
joshualevy

Cort, I think you are making a mistake when you say:

The most significant result may have been the quite strong finding (P<.0002) that longer treatment durations (7.4 months on average) resulted in improved benefits relative to shorter treatment durations (5.5 months). Long antiviral treatment regimes are a key feature of Dr. Lerner's antiviral treatment protocol.

Here are two possible source for this "longer treatment means bigger improvements" result:

Trough vs Peak differences will get bigger (on average) for longer study duration, if you are reporting only on peak results. This result could easily be a direct effect of the reporting design, where only peak results are reported. Basically, the longer duration gives more time for a randomly higher peak to be seen and reported.

Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news.

Other random points:
I think it's pretty clear that this research has failed, or is in deep-deep trouble.
Why? Because successful research moves forward. If a researcher does a successful intervention study with 12 people and no placebo, then the next experiment will be an intervention study with more than 12 people and/or a placebo group, and almost certainly both.

This research program took several steps backward. First: The earlier study was intervention, and the later study was population based, that's a HUGE step backward. Second: While it is ok for the first study is a research program to be no-placebo, once you have good results from that, the follow on studies should have a control group of some kind.

Also, using "peak scores" results for a disease like ME/CFS where patients are known to go through better and worse phases, is a major design flaw. It completely negates any results (my opinion, of course). What possible motivation could there be for a design like that, in a disease like this?

Remember, the drug Drs. Kogelnik and Montoya are testing is produced by some Pharma company. That company would love to sell it to millions of ME/CFS sufferers. So there should be plenty of money available to fund a follow-on study to expand the use of a drug. So whatever the problem, it's not a lack of funding.

Joshua (not Jay) Levy

"Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news."

False. Absolutely backwards. Look at the research on placebo vs active drug in conditions like depression that respond well to placebo. Placebo effects are mediated by expectations (and neurologically by release of endogenous opioids and other rewarding brain chemicals), and they are at their greatest strength early in the course of a treatment when the treatment is novel. (i.e. after you've been doing something for six months, and nothing has changed, its hard to particularly get your hopes up and change your behavior then..)

ME/CFS has a lower placebo response rate than most other medical conditions. It is very, very difficult to treat by any means.

I think "regression to the mean" is a more significant problem than placebo in ME/CFS treatment effects. This is because the illness has fluctuating symptoms. Patients may start a new therapy when they are feeling really desperate, then they "improve" over time but are really just going back to their average level of sickness. At some point they hit a wall again and the cycle repeats. This behavior pattern is what I see with a lot of the patient reports on forums. Patients are very prone to changing things when they are in a relapse, and not prone to change things when they are in remission. It's a problem.

heapsreal November 23, 2012 at 9:48 pm

i wouldnt think placebo effects would last. For what its worth my t cells improved with antivirals so placebo wouldnt affect that?

joshualevy November 23, 2012 at 11:32 pm

I wrote this:
"Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news."

satoshikasumi

False. Absolutely backwards. Look at the research on placebo vs active drug in conditions like depression that respond well to placebo. Placebo effects are mediated by expectations (and neurologically by release of endogenous opioids and other rewarding brain chemicals), and they are at their greatest strength early in the course of a treatment when the treatment is novel. (i.e. after you've been doing something for six months, and nothing has changed, its hard to particularly get your hopes up and change your behavior then..)

heapsreal

i wouldnt think placebo effects would last. For what its worth my t cells improved with antivirals so placebo wouldnt affect that?

Well, there are different placebo effects based on the psychology of the patients involved. I'm sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result.

But since the research are reporting only peak response (not average response, or longest lasting response, or more recent response), they would mis-report both placebo effects.

Heapsreal: this is why it doesn't matter how long the effect lasts. If some thinks it worked great the day after, then that will be the peak response, and the only thing reported, even if they later come to believe it did nothing.

Cort, I had the following question: how did they report bad side effects? Did they report them? Did they provide more details than the PACE report, or less? Reporting peak good response sounds highly biased to me, so I'm a little interested in how they counted bad effects, although with no control group, it would be hard to tell how important these would be.

Joshua (not Jay) Levy

.

Firestormm November 24, 2012 at 2:34 am
Simon

Thanks for another great piece, Cort: its thorough, fair and a little depressing.

It's extraordinary that six years after a highly promising finding we still don't have a decent placebo-controlled study to properly evaluate the treatment.

There is a separate thread on this study, including some excellent analysis by Dolphin. This highlights issues raised by the study itself that they used peak scores – which may have come a long time after treatment was discontinued, suggesting the treatment may not be related to the improvement. Worse, the use of peak scores means that any patients with fluctuating scores will appear to improve since the highest peak will be recorded, while troughs will be ignored.

Montoya['s] reportedly been plowing through immune findings to see if he can pick up measurements that change significantly as people get well

That sounds alarmingly like data mining: your main hypothesis (high antibody titres) flops so you search through data for until you find an association that looks significant. Except if you search through enough possibilities, you'll find several 'significant' associations just by chance. Surely, after so many years working on this, if there was a genuine strong association then Montoya would have already found it?

Maybe one of Montoya's oft-promised studies will finally materialise and lift my gloom.

Thanks Simon. It rather reminds me of the Ampligen last 'mining' episode. I can't imagine why – other than funding – a properly blinded study has not been forthcoming with acceptable representation of data before now.

Cort's piece is well-balanced – thankfully. When this latest was published back in October it was to the casual observer (i.e. me at the time) 'promising'. I do wish they wouldn't do this.

The headline and extract grabs the headline – the content gets assessed by others in the know – and then the 'hope' gets screwed.

I know the answer – but I can't help asking – is it only ME/CFS studies that do this?

Why-oh-why aren't these original findings built on properly using the funds that are available instead of them phaffing around like this.

It will only get cited by someone claiming it represents legitimacy only for them to be shot down by those who understand what this latest and former one means.

Depressing? Yes. Yet another small original study that I can only file away as 'interesting' along with several hundred others – never to see the light of day. [Sigh]

satoshikasumi November 24, 2012 at 8:23 am
joshualevy

I wrote this:
"Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news."

satoshikasumi

False. Absolutely backwards. Look at the research on placebo vs active drug in conditions like depression that respond well to placebo. Placebo effects are mediated by expectations (and neurologically by release of endogenous opioids and other rewarding brain chemicals), and they are at their greatest strength early in the course of a treatment when the treatment is novel. (i.e. after you've been doing something for six months, and nothing has changed, its hard to particularly get your hopes up and change your behavior then..)

heapsreal

i wouldnt think placebo effects would last. For what its worth my t cells improved with antivirals so placebo wouldnt affect that?

Well, there are different placebo effects based on the psychology of the patients involved. I'm sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result.

But since the research are reporting only peak response (not average response, or longest lasting response, or more recent response), they would mis-report both placebo effects.

Heapsreal: this is why it doesn't matter how long the effect lasts. If some thinks it worked great the day after, then that will be the peak response, and the only thing reported, even if they later come to believe it did nothing.

Cort, I had the following question: how did they report bad side effects? Did they report them? Did they provide more details than the PACE report, or less? Reporting peak good response sounds highly biased to me, so I'm a little interested in how they counted bad effects, although with no control group, it would be hard to tell how important these would be.

Joshua (not Jay) Levy

.

"Well, there are different placebo effects based on the psychology of the patients involved. I’m sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result."

This argument contradicts the lived experience of every patient with bona-fide ME/CFS and requires the assumption that post-exertional malaise is not a real, biological phenomenon. It also contradicts the research on post-exertional malaise from the Pacific Fatigue Lab, the research on the long-term effects of CBT/GET that has come out of the Netherlands and other countries that had committed to a psychological approach, research on the extent of the disability in ME/CFS, research on the long-term outcome and recovery rate in ME/CFS, and the only study to estimate the placebo effect in ME/CFS.

I can't vouch for every patient on these forums, but my commitment, belief in a better future, optimism, trust in my doctor and the treatments; none of this was enough to improve my illness or allow me to live a normal life again.

Why didn't the placebos work for me in the first seven years of my illness? In the first two years, especially, I really believed I was going to get better soon.. I had that expectation and I thought I could figure out how to bring it under control, with the help of my doctor. In the first four years, I tried every permutation of exercise and psychotherapy known to man. I followed the official guidelines and tried long courses of biologically plausible treatments that made sense to me- drugs for orthostatic intolerance, sleep, stimulants, long-term antibiotics and antivirals, immune-boosting supplements. But none of this worked. Doing nothing didn't work either. I just kept getting more disabled over time. My anaerobic threshold and VO2 max scores kept falling.

Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.

heapsreal November 24, 2012 at 3:41 pm

If it was all about placebo then many of us would have been cured by the mountains of supps from iherb. Different treatments work for different people some of the time mainly because its guess work in which treatment is right for which patient. I dont think we are going to get away from sub groups, until someone can nail down the specific sub group one is in, then its an educated guess when we treat cfs/me.

There seems to be some people refusing to believe people get better with certain treatments but the fact is that some are getting better with certain treatments and i dont think its placebo and many have testing which correlates with their improvement. Theres no silver bullet for everyone and there is probably a certain number that wont improve with any type of treatments but there are also many that do improve if they have the right treatment for them.

In the early days of myself using antivirals, i stopped and started them as i couldnt quite believe it was helping, i thought maybe i was just naturally improving, but whenever i stopped i got worse and up went my lymphocytes. Back on antivirals down went my lymphocytes and i started to feel better.

If someone tells me they got better on vitamin c then good on them, pointless saying that they done have cfs/me etc maybe vit c was that one thing they needed. theres no way to really diagnose cfs/me but we can treat abnormalities found in testing and its a load of crap when they say testing incfs is normal, that just means your doctor isnt doing the right tests.

Stukindawski November 24, 2012 at 6:52 pm
satoshikasumi

Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.

I'm curious, between the time you took Ampligen and the increase in your V02 max, had you done much additional exercise (more than you would do before Ampligen) prior to the test?

I don't mean to undermine anything, but I think a great test of treatment response would be the V02 max threshold increasing, after treatment with zero activity increase in between. This kind of evidence would make any reasonable level of improvement significant in my opinion.

Cort November 25, 2012 at 9:23 am
Simon

Thanks for another great piece, Cort: its thorough, fair and a little depressing.

It's extraordinary that six years after a highly promising finding we still don't have a decent placebo-controlled study to properly evaluate the treatment.

There is a separate thread on this study, including some excellent analysis by Dolphin. This highlights issues raised by the study itself that they used peak scores – which may have come a long time after treatment was discontinued, suggesting the treatment may not be related to the improvement. Worse, the use of peak scores means that any patients with fluctuating scores will appear to improve since the highest peak will be recorded, while troughs will be ignored.

That sounds alarmingly like data mining: your main hypothesis (high antibody titres) flops so you search through data for until you find an association that looks significant. Except if you search through enough possibilities, you'll find several 'significant' associations just by chance. Surely, after so many years working on this, if there was a genuine strong association then Montoya would have already found it?

Maybe one of Montoya's oft-promised studies will finally materialise and lift my gloom.

I think it was in December of 2010 that Montoya promised several studies and that this one would be the first and the placebo-controlled one was in that package..My guess is that there is a strong association in there but in fewer patients than expected and ferreting them out may be difficult..

Yes, the time element is troubling but even this paper took about a year longer, if I have my dates right, than expected. Its possible that Montoya is balancing many plates and its going to take longer than expected for that second study to come out. I imagine it will come out at some point and then we'll see. I would not expect something earth shattering but I wouldn't expect a total loss either – I would expect some good news for some patients…just not as many as hoped for.

Everybody who studies this disorder ends up concluding its much more complex than they originally thought.

Cort November 25, 2012 at 9:34 am
satoshikasumi

"Well, there are different placebo effects based on the psychology of the patients involved. I’m sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result."

This argument contradicts the lived experience of every patient with bona-fide ME/CFS and requires the assumption that post-exertional malaise is not a real, biological phenomenon. It also contradicts the research on post-exertional malaise from the Pacific Fatigue Lab, the research on the long-term effects of CBT/GET that has come out of the Netherlands and other countries that had committed to a psychological approach, research on the extent of the disability in ME/CFS, research on the long-term outcome and recovery rate in ME/CFS, and the only study to estimate the placebo effect in ME/CFS.

I can't vouch for every patient on these forums, but my commitment, belief in a better future, optimism, trust in my doctor and the treatments; none of this was enough to improve my illness or allow me to live a normal life again.

Why didn't the placebos work for me in the first seven years of my illness? In the first two years, especially, I really believed I was going to get better soon.. I had that expectation and I thought I could figure out how to bring it under control, with the help of my doctor. In the first four years, I tried every permutation of exercise and psychotherapy known to man. I followed the official guidelines and tried long courses of biologically plausible treatments that made sense to me- drugs for orthostatic intolerance, sleep, stimulants, long-term antibiotics and antivirals, immune-boosting supplements. But none of this worked. Doing nothing didn't work either. I just kept getting more disabled over time. My anaerobic threshold and VO2 max scores kept falling.

Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.

I took tried everything I could think of and had faith in many but had no effects from any treatments – bad or good for the first 10 years. That said I think I can harness the effects of placebo now….that is, for some reason, being relaxed and at ease and hopeful really do help now….I can see how stress really discombulates my system….

Until a rigorously designed blinded, placebo-controlled trial pops up though the placebo effect, particularly in this illness with all its controversy, will probably be highly entertained by many, even if past research suggests not. ..

I think we should keep in mind that Montoya is not primarily a researcher – he's a physician/researcher – his publication list is not that long or involved….so while I agree that six years is alarming and it must indicate that the results have not been straightforward, it'll probably take him longer to publish than straight researchers.

Cort November 25, 2012 at 9:41 am

Dr. Lerner's protocol is a good example of the need to isolate factors. Dr. Lerner uses long term antiviral therapy but he is also adamant that his patients practice rigorous pacing…….which could lead some to posit that its the pacing that's doing it not the antiviral therapy.

Should antiviral therapy be able to work without pacing?..Does it require pacing or does not pacing just make it more difficult and take it longer for the antivirals to work?

It would take a separate pacing/placebo arm and a separate pacing/antiviral arm to ferret this out and that would be difficult because of the long time frames for his therapy and THAT is another problem…Doing a study of a year long or more length…

This is unusual stuff for the medical community. Herpesvirus antivirals are almost always taken short term not long term and certainly not the really long term, high dose protocols that Dr. Lerner uses. Those protocols have lead to him being characterized by some in the medical community as a quack. I've gotten several recovery/recovering stories from patients of his who said they were vigorously warned away from Dr. Lerner by other doctors only to find that his protocol worked for them.

Dr. Lerner's and Dr. Montoya's view of ME/CFS and herpesvirus infections bucks trends………

The significance value of the long term duration benefits was rather high which was encouraging….the measurement of effects, however, was really poor – relying on a vague assessment and then they picked the highest values – obviously because the averages did not work out….

Cort November 25, 2012 at 9:53 am
Stukindawski

I'm curious, between the time you took Ampligen and the increase in your V02 max, had you done much additional exercise (more than you would do before Ampligen) prior to the test?

I don't mean to undermine anything, but I think a great test of treatment response would be the V02 max threshold increasing, after treatment with zero activity increase in between. This kind of evidence would make any reasonable level of improvement significant in my opinion.

heapsreal

it would be interesting to see a study where they also test nk and cd8 function in those patients as well as compare antivirals with combo of antiviral and immune mod with a placebo treatment and seeing the before and after results of viral titres , nk and cd8 function. Im suprised further sudies havent been done but then alot also depends on drug companies and patents for new indications etc.

cheers!!!

If the placebo controlled study was done my understanding is that they were doing immune tests, aerobic functioning tests, brain imaging tests…..lots of stuff….

Cort November 25, 2012 at 10:10 am

Maybe we should call this the Montoya Lag

This is from the post in Dec 2010 which talked about what they were doing…(see below)

  • Two papers on the double-blinded Valcyte trials had been or were in the process of wrapping up
  • A paper (probably this one) that indicated that viral titers (not antibodies?) responded to Valcyte
  • A conference presentation suggesting that Dr. Montoya had discovered immune factors that several immune markers (IL5, IL17F, ENA78, EOTAXIN, IP10) improved during treatment
  • Exciting brain MRI findings
  • Lipkin pathogen study
  • EEG and exercise findings
  • Major research meeting

That was two years ago…Since then we have this paper and he participated in the XMRV study. Dr. Montoya reportedly dropped out of the Lipkin study. If he was overcommitted that's the one I would have dropped out of….
Is this a case of researcher overreach? It seems that researchers rarely make their projected due dates…(The CAA's gut metabiome study and Dr. Baraniuk's spinal fluid studies spring to mind.)….or are these projects stalled or not working out….I am going to try and ask…
Montoya has actually been publishing more than usual in the last year or so – just not so much in CFS….

Recent work - they have recently wrapped up a number of longstanding projects and have or are submitting the results for publication. These include two papers on the double-blinded Valganciclovir trials in EBV and HHV-6 positive ME/CFS patients that started some years ago. Another paper indicating both that clinical (symptoms) and viral titers responded to antiviral treatment in HHV-6 infected patients should be in press in the not too distant future.
(Interlude: Barcelona Conference - According to a report on the internet http://pochoams.blogspot.com/2010/11…-november.html in November Dr. Montoya presented evidence suggesting that monocytes may key a role in this type of ME/CFS patient and that several immune markers (IL5, IL17F, ENA78, EOTAXIN, IP10) improved during treatment – a potential breakthrough in demonstrating the legitimacy of antiviral treatment (and the disorder itself). He has also found that an early antigen marker usually associated with cancer may be a biomarker for this group, that HHV6 integrates into the chromosome of CFS patients, which is apparently not normal for this virus. (Viral integration into the chromosomes means that when the cell replicates the virus replicates as well).
Current Work:
The Big Pathogen Study – They are currently collaborating with Dr. Lipkin and other colleagues on a comprehensive analysis of the pathogens in ME/CFS

[​IMG]

Immune Signatures - They are analyzing the immune response using gene expression, cytokine profiles and phosph immune-flow to look for biomarkers and immune signatures correlated with these infections. These biomarkers could be used both to diagnose and to assess improvements during treatment.
Biomarkers in the Brain – Finally? – in a novel approach that reminds one of the attempts to correlated MRI findings with disease early on in the history of CFS, the Montoya team is doing sophisticated new MRI techniques to see if they can use brain imagining to identify unique abnormalities in infected individuals. Several of these pathogens are able to access the central nervous system.
A New Website - a new website explaining their work should be open early next year and a patient forum has been set up.
Quantifying Impairment -Legitimizing ME/CFS - they are also using sub-maximal exercise testing and EEG readings to quantify (and make real) the physical and cognitive impairments in ME/CFS.
Education and Outreach

  • A Major Research Meeting – will be held to change information on and educate investigators on ‘chronic inflammatory diseases.
  • Biennial Education Meeting – will educate researchers, students, etc. on their progress

satoshikasumi November 25, 2012 at 11:12 am
Stukindawski
satoshikasumi

Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.

I'm curious, between the time you took Ampligen and the increase in your V02 max, had you done much additional exercise (more than you would do before Ampligen) prior to the test?

I don't mean to undermine anything, but I think a great test of treatment response would be the V02 max threshold increasing, after treatment with zero activity increase in between. This kind of evidence would make any reasonable level of improvement significant in my opinion.

I did not have my activity levels monitored before and during Ampligen treatment; actigraphy was not commonly used in ME/CFS studies at that time, and still isn't used enough.

I think what you are getting at is whether the increase might result from training. I'm not sure your assumption that training will increase the VO2 Max in ME/CFS is correct. I was one of those people who made all efforts to stay active after my diagnosis. I was diagnosed early.

When my illness was first diagnosed, I had only mild disability and my symptoms were mostly cognitive; in May 2003 my VO2 max was 42 ml/kg/min, which was in the low normal range for a 20 year old man (age predicted median is 48 with a standard deviation of 7).

Reading and actually believing the studies about graded exercise being helpful, I continued to do 20 minutes of moderate-intensity bike riding twice a day, five days a week. Over the ensuing year I did not stop the bike riding, regardless of symptoms. I slowly deteriorated and was having to spend more and more time in bed when I wasn't exercising, and my orthostatic intolerance and cognitive problems (such as difficulty reading and memory loss) kept getting worse and worse. I retook the VO2 max test in March 2004 and my VO2 max was 23.8 ml/kg/min, more than three standard deviations below age norms. I eventually was not able to do the bike riding anymore in mid-2004, but I continued to walk and do lighter forms of exercise as I was able. My ability to work never returned until I took Ampligen. The lowest my VO2 max got was 19 ml/kg/min, which met the SSDI disability criterion.

When I started Ampligen, my VO2 max rose to 25.9 ml/kg/min within 8 months and was 31 ml/kg/min a year after stopping the drug. I was relatively sedentary during Ampligen, more cautious with exercise by this point, but continued to walk regularly.

Look, many people in America are very sedentary. They never ride their bikes or walk like I did. But they never suffer a catastropic decrease in VO2 max like I did. The CBT/GET theory is simply wrong. No matter how much exercise you do and how good you are at persistence and toughing out the pain, it will not improve functional capacity if you have this disease.

Stukindawski November 25, 2012 at 11:52 am
satoshikasumi

I did not have my activity levels monitored before and during Ampligen treatment; actigraphy was not commonly used in ME/CFS studies at that time, and still isn't used enough.

I think what you are getting at is whether the increase might result from training. I'm not sure your assumption that training will increase the VO2 Max in ME/CFS is correct. I was one of those people who made all efforts to stay active after my diagnosis. I was diagnosed early.

When my illness was first diagnosed, I had only mild disability and my symptoms were mostly cognitive; in May 2003 my VO2 max was 42 ml/kg/min, which was in the low normal range for a 20 year old man (age predicted median is 48 with a standard deviation of 7).

Reading and actually believing the studies about graded exercise being helpful, I continued to do 20 minutes of moderate-intensity bike riding twice a day, five days a week. Over the ensuing year I did not stop the bike riding, regardless of symptoms. I slowly deteriorated and was having to spend more and more time in bed when I wasn't exercising, and my orthostatic intolerance and cognitive problems (such as difficulty reading and memory loss) kept getting worse and worse. I retook the VO2 max test in March 2004 and my VO2 max was 23.8 ml/kg/min, more than three standard deviations below age norms. I eventually was not able to do the bike riding anymore in mid-2004, but I continued to walk and do lighter forms of exercise as I was able. My ability to work never returned until I took Ampligen. The lowest my VO2 max got was 19 ml/kg/min, which met the SSDI disability criterion.

When I started Ampligen, my VO2 max rose to 25.9 ml/kg/min within 8 months and was 31 ml/kg/min a year after stopping the drug. I was relatively sedentary during Ampligen, more cautious with exercise by this point, but continued to walk regularly.

Look, many people in America are very sedentary. They never ride their bikes or walk like I did. But they never suffer a catastropic decrease in VO2 max like I did. The CBT/GET theory is simply wrong. No matter how much exercise you do and how good you are at persistence and toughing out the pain, it will not improve functional capacity if you have this disease.

My scepticism has a bias in that, I'd like to prove you right heh. I'm particularly interested in V02 max at the moment. I gather someone like Dr Klimas might argue that your 20 minute bike riding took you into anaerobic respiration and the decline is consistent with that (which appears based on Dr Klimas and Professor Newton's work, to be a destructive factor in CFS).

Their belief holds that a small amount of exercise, really small, that respects the patient's aerobic limits may recondition the body to some degree. I guess what I'm looking for is an absolute gold standard of proof, which shows the Ampligen interfering (via inteferon – *ahem*) with the neurological condition that in my vague hypothesis, caused your decline in vo2 max threshold.

satoshikasumi November 25, 2012 at 12:15 pm

I think skepticism is warranted, but not the stifling kind of skepticism that squelches research and prevents it from moving forward.

Since there is a lack of Federal funding, the best way to make sure your gold standard research gets done would be for the FDA to give provisional approval to Ampligen and make full approval conditional on a much more thorough vetting of the drug's efficacy and mechanism of action.

Hemispherx has the only viable drug candidate with patent protection for ME/CFS at this point. But the company is nearly bankrupt; the drug was invented in the 1970s. The only way we are going to know more about it is to make it more widely available.

Anne November 25, 2012 at 1:16 pm

Thanks for this, Cort, another great post and discussion.

"Everybody who studies this disorder ends up concluding its much more complex than they originally thought."

So true!!

"It seems that researchers rarely make their projected due dates…(The CAA’s gut metabiome study and Dr. Baraniuk’s spinal fluid studies spring to mind.)….or are these projects stalled or not working out….I am going to try and ask…"

Just what I thought. Where IS the Baraniuk study…??

Thanks for keeping us up to date. More posts please!! :-)

heapsreal November 25, 2012 at 4:26 pm

Thats a big difference when we talk about viral titres, antibody titres are dependent on a healthy immune system. So viral titres coming down with improvement is a good indicator that the viruses have a large role in these viral sub groups. Very interesting, thanks for posting this cort.

vli November 25, 2012 at 5:04 pm
heapsreal

Thats a big difference when we talk about viral titres, antibody titres are dependent on a healthy immune system. So viral titres coming down with improvement is a good indicator that the viruses have a large role in these viral sub groups.

AMEN!!!

Cort November 25, 2012 at 6:09 pm
Anne

Thanks for this, Cort, another great post and discussion.

"Everybody who studies this disorder ends up concluding its much more complex than they originally thought."

So true!!

"It seems that researchers rarely make their projected due dates…(The CAA’s gut metabiome study and Dr. Baraniuk’s spinal fluid studies spring to mind.)….or are these projects stalled or not working out….I am going to try and ask…"

Just what I thought. Where IS the Baraniuk study…??

Thanks for keeping us up to date. More posts please!! :)

Dr. Baraniuk put out some abstracts at the Ottawa conference last year and told me the papers would start flooding our over the next year….(He felt he would get quite a few papers out of it.) At least that's what I remember. I guess its going to be 2013…

heapsreal November 25, 2012 at 6:41 pm

Cort,
Is there any news on valcyte becoming generic, outside of india as i think they have ignored the patent. i suppose so its more affordable to more of the cfs/me community. Also any News on peterson and the antiviral cmx(ithink thats what its called) or any other new antivirals being developed for these herpes viruses.

Cort November 26, 2012 at 3:31 pm
heapsreal

Cort,
Is there any news on valcyte becoming generic, outside of india as i think they have ignored the patent. i suppose so its more affordable to more of the cfs/me community. Also any News on peterson and the antiviral cmx(ithink thats what its called) or any other new antivirals being developed for these herpes viruses.

Don't know about valcyte but the CMX001 trial just pooped out. It sounded like Dr. Peterson just stopped hearing from them…and they lost interest or went in another direction…Hopefully the drug will get approved for something and then it will be available for use in ME/CFS.

They are moving forward…They've complete a couple of trials…

This is what their website says…

Chimerix has established a pipeline of therapeutics addressing life-threatening viral diseases. Our lead compound, CMX001, is currently being developed to treat dsDNA viruses – potentially deadly diseases for immunocompromised patients. A second compound, CMX157, is being advanced to treat human immunodeficiency virus (HIV). In addition, we have identified highly active compounds against hepatitis C and influenza. We are also screening our proprietary Chimerix Chemical Library for compounds with activity against dengue virus, malaria and tuberculosis.

CMX001-201 Phase 2 Trial
CMX001 has completed a Phase 2 randomized, double-blind, placebo-controlled, dose-escalation study designed to assess the safety, tolerability and ability of CMX001 to prevent or control cytomegalovirus (CMV) infection in 230 hematopoietic cell transplant (HCT) recipients (Study 201). CMV, a member of the herpesvirus family of dsDNA viruses, is present in more than two-thirds of the population and typically causes manageable disease in individuals with responsive immune systems. However, in immunosuppressed and immunocompromised transplant recipients, CMV is a major cause of morbidity and mortality.
CMX001-202 Phase 2 Trial (AdV HALT Trial)
CMX001 is being studied in a randomized, placebo-controlled, Phase 2 trial evaluating the safety and efficacy of preemptive treatment with CMX001 versus placebo for the prevention of adenovirus (AdV) disease in 48 pediatric and adult hematopoietic cell transplant (HCT) recipients with asymptomatic AdV viremia (Study 202). Adenoviruses are responsible for respiratory diseases, including pneumonia and bronchitis, as well as other infections, including gastroenteritis and acute diarrheal diseases. In immunocompromised patients who have undergone HCT, AdV infections are recognized as a significant cause of morbidity and mortality. Immunocompromised pediatric HCT patients are particularly susceptible to serious and/or fatal AdV infections. The U.S. FDA has granted CMX001 Fast Track designation status for the AdV development program.
CMX157
CMX157 demonstrated a favorable safety, tolerability and drug distribution profile in a first-in-human clinical trial. The Phase 1 study was a randomized, blinded, single dose, dose-escalation trial to evaluate safety, tolerability and pharmacokinetics of CMX157 in healthy volunteers.

Cort November 26, 2012 at 3:35 pm
Cort

Don't know about valcyte but the CMX001 trial just pooped out. It sounded like Dr. Peterson just stopped hearing from them…and they lost interest or went in another direction…Hopefully the drug will get approved for something and then it will be available for use in ME/CFS.

They are moving forward…They've complete a couple of trials…

This is what their website says…

Chimerix has established a pipeline of therapeutics addressing life-threatening viral diseases. Our lead compound, CMX001, is currently being developed to treat dsDNA viruses – potentially deadly diseases for immunocompromised patients. A second compound, CMX157, is being advanced to treat human immunodeficiency virus (HIV). In addition, we have identified highly active compounds against hepatitis C and influenza. We are also screening our proprietary Chimerix Chemical Library for compounds with activity against dengue virus, malaria and tuberculosis.

CMX001-201 Phase 2 Trial
CMX001 has completed a Phase 2 randomized, double-blind, placebo-controlled, dose-escalation study designed to assess the safety, tolerability and ability of CMX001 to prevent or control cytomegalovirus (CMV) infection in 230 hematopoietic cell transplant (HCT) recipients (Study 201). CMV, a member of the herpesvirus family of dsDNA viruses, is present in more than two-thirds of the population and typically causes manageable disease in individuals with responsive immune systems. However, in immunosuppressed and immunocompromised transplant recipients, CMV is a major cause of morbidity and mortality.
CMX001-202 Phase 2 Trial (AdV HALT Trial)
CMX001 is being studied in a randomized, placebo-controlled, Phase 2 trial evaluating the safety and efficacy of preemptive treatment with CMX001 versus placebo for the prevention of adenovirus (AdV) disease in 48 pediatric and adult hematopoietic cell transplant (HCT) recipients with asymptomatic AdV viremia (Study 202). Adenoviruses are responsible for respiratory diseases, including pneumonia and bronchitis, as well as other infections, including gastroenteritis and acute diarrheal diseases. In immunocompromised patients who have undergone HCT, AdV infections are recognized as a significant cause of morbidity and mortality. Immunocompromised pediatric HCT patients are particularly susceptible to serious and/or fatal AdV infections. The U.S. FDA has granted CMX001 Fast Track designation status for the AdV development program.
CMX157
CMX157 demonstrated a favorable safety, tolerability and drug distribution profile in a first-in-human clinical trial. The Phase 1 study was a randomized, blinded, single dose, dose-escalation trial to evaluate safety, tolerability and pharmacokinetics of CMX157 in healthy volunteers.

Here's a list of past or present trials involving CMX 001 from clinicaltrials.gov

Not yet recruiting A Multiple Ascending Dose-Finding Pharmacokinetic and Pharmacodynamic Study of CMX-001 in Infants With Neonatal Herpes Simplex Virus (HSV)
Condition: Herpes Simplex Virus
Interventions: Drug: CMX 001; Drug: Placebo

2 Completed Comparative Bioavailability and Effect of Food on CMX001 in Healthy Volunteers
Condition: Healthy
Intervention: Drug: CMX001

3 Completed CMX001 in Post-transplant Patients With BK Virus Viruria
Condition: Viruria
Interventions: Drug: Placebo; Drug: CMX001

4 Active, not recruiting A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by dsDNA Viruses
Conditions: Male or Female Patients With a Serious or Immediately Life-threatening; Disease or Condition Caused by CMV, ADV, HSV, VAVC, VARV or; Monkeypox Viruses(s) Who Have a Life Expectancy of ≥ 2 Weeks and for; Whom no Comparable or Satisfactory Alternative Therapy is Available
Intervention: Drug: CMX001

5 Recruiting The Adv Halt Trial
Condition: Adenovirus Disease
Intervention: Drug: CMX001

6 Completed Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control Cytomegalovirus (CMV) Infection in R+ Hematopoietic Stem Cell Transplant Recipients
Condition: Cytomegalovirus Infection
Interventions: Drug: CMX001; Drug: Placebo

Sushi November 26, 2012 at 5:40 pm

Cort
So it doesn't look like there is any avenue for us to get into one of these trials?!

Dr. Kogelnik was trying too I think.

Sushi

Hope123 November 27, 2012 at 4:35 am

Cort, it's late and I did a quick read of the paper but I think your statement about all subjects having "high" titers (as they defined it) is incorrect.

I see this papers as an attempt to make use of all the data they have; outside of the Valganciclovir trial, some patients were getting treated on an individual clinic basis (i.e. not in a study) who did not fit the definition of high titers from the first randomized trial although some did. Inclusion criteria for this paper's patients did not include a particular level of titers. (just Fukuda/ Valcyte treatment/ and titer/ self-report availability were used as inclusion) Those who did fit the "high" titers were classified as "high" here and their responses were compared to those who did not fit (i.e. lower titers or did not have all "high" values). So the surprise was that even people WITHOUT high titers were just as likely to respond (62% high vs. 41% low) and respond the same degree as those with "high" titers. [The differences were statistically non-signficant.]

This issue with what Tom pointed out — this is what is technically called "absolute" vs. "relative" difference. So the change in physical status from 34% to 53% — 19% (53-34)) is the absolute difference whereas 56% (e.g. 19%/ 34%) is the relative. In some research circles, the trend is going away from using relative difference since it can be misleading and that is prob. why they use absolute instead. For example, saying exposure to XYZ substance leads to a tripling of risk of cancer sounds scary until you realize the tripling (relative) is from 0.00001% to 0.00003%. Absolute diff here would be 0.00002%.

In terms of them using the highest physical/ cognitive function as the outcome, it can be debated whether that is the best outcome measure but other studies, including the Norwegian rituxmab trial, also used maximum improvement. The problem is that subjects improved/ disimproved at different times and different rates.

Cort November 27, 2012 at 7:12 am
Hope123

Cort, it's late and I did a quick read of the paper but I think your statement about all subjects having "high" titers (as they defined it) is incorrect.

I see this papers as an attempt to make use of all the data they have; outside of the Valganciclovir trial, some patients were getting treated on an individual clinic basis (i.e. not in a study) who did not fit the definition of high titers from the first randomized trial although some did. Inclusion criteria for this paper's patients did not include a particular level of titers. (just Fukuda/ Valcyte treatment/ and titer/ self-report availability were used as inclusion) Those who did fit the "high" titers were classified as "high" here and their responses were compared to those who did not fit (i.e. lower titers or did not have all "high" values). So the surprise was that even people WITHOUT high titers were just as likely to respond (62% high vs. 41% low) and respond the same degree as those with "high" titers. [The differences were statistically non-signficant.]

This issue with what Tom pointed out — this is what is technically called "absolute" vs. "relative" difference. So the change in physical status from 34% to 53% — 19% (53-34)) is the absolute difference whereas 56% (e.g. 19%/ 34%) is the relative. In some research circles, the trend is going away from using relative difference since it can be misleading and that is prob. why they use absolute instead. For example, saying exposure to XYZ substance leads to a tripling of risk of cancer sounds scary until you realize the tripling (relative) is from 0.00001% to 0.00003%. Absolute diff here would be 0.00002%.

In terms of them using the highest physical/ cognitive function as the outcome, it can be debated whether that is the best outcome measure but other studies, including the Norwegian rituxmab trial, also used maximum improvement. The problem is that subjects improved/ disimproved at different times and different rates.

You're right – my mistake…I said all patients had above normal titers but that wasn't true…Dr. Montoya's thesis has been that high titers in presence of certain symptoms is suggestive of active infection but here we find that antibody titer level at baseline is not significantly associated with treatment response.

They also used the highest titer prior to the start of the trial rather than an average or the most recent measurement..Then they say that EBV titers are remarkably stable over time…which makes one wonder why they had to pick the highest one…In any case, it appears that alot of 'work' went into making this study as positive as possible.

titer within 1 year prior to starting treatment. The highest titers prior to treatment (rather than the average of all available titers) were chosen because high titers of a certain threshold were considered to have the greatest pathological impact and because EBV titers have been shown to be remarkably stable over long-term follow-up of healthy individuals [Amanna et al., 2007]. Final titers were defined as those closest to the cessation of treatment but no later than 6 months after stopping treatment. If no such value

Thanks for explaining why they choose to use absolute difference instead of relative..In that case they chose a method which did not shed a more positive light on their results (even though to me it would have made sense to do so )

Enid November 27, 2012 at 8:05 am

Thanks Cort – very encouraging following the research coming out here. Looking forward to some conclusion on brain imaging (mine abnormal – high spots/lesions whatever) if they are included.

Cort November 27, 2012 at 12:14 pm

Look at this study…

4 Active, not recruiting A Multicenter, Open-label Study of CMX001 Treatment of Serious Diseases or Conditions Caused by dsDNA Viruses
Conditions: Male or Female Patients With a Serious or Immediately Life-threatening; Disease or Condition Caused by CMV, ADV, HSV, VAVC, VARV or; Monkeypox Viruses(s) Who Have a Life Expectancy of ≥ 2 Weeks and for; Whom no Comparable or Satisfactory Alternative Therapy is Available

It looks almost like last-ditch efforts for some of these folks. You can see looking at the list that it's perhaps not surprising that Chimerix pulled out of Dr. Peterson's trial; Chimerix is focusing on pretty well defined and accepted problems….ie transplant patients and these folks…I'm sure some ME/CFS patients could fit into this study via the CMV route…but HHV6 is not there and neither is EBV and Peterson sees more of those than CMV…The adenovirus trial is ending this January….

MARGARITA COLOMBO November 27, 2012 at 10:14 pm

Please, read my post. I am not so informed like you all for getting into a deep detailed discussion, I have followed a more simplistic way of investigating all about my health condition, but for a long time I got very good results. Even that, if I were to participate in any medical protocol, I would definitely go for Montoya´s aproach. Viruses, bacteria and fungus are in the bottom line of this, as well as our inmunologic system.
When I had excelent results for my phisical state I went from no exercise at all in 15 years to runing from 3 to 4 kms every other day and runing a 6 kms race for the first time in my whole life. Even though my problems began many years ago, they got acute with Herpes-2 infection when I got married, 20 years ago. So I believe that the issue is not one sigle microorganism, but the agregation of them, or the imbalance betwenn microorganisms and our inmune system.

Nutritional and alternative protocols, trying to have a healthy holistic life help by improving our inmune system, balance and equilibrium is important: too much exercise is as bad as none. Staying in bed is as bad as going to bed too late. Etc. ( All this is HIGLY IMPORTANT to control in scientific trials because a disfunctional nervous system is very much energy-drained for little adaptations!). One single day staying late in the computer and my sugar level next day is out of control, in normal people this happens after many nights, we have very strong changes after very little efforts.

Antivirals are an extra help for our body for controlling viruses, like antifungals and antibiotics, but they also have downsides, like killing our friendly bacteria in the gut, making us more constipated or the contrary, etc.

I hope you don´t mind reading this very plain text, but I thing that sometimes we underestimate simple things, and we fall into microscopic problems, medical terms, etc., and we fail in observing little things…

One single glass of wine can lead me to 3 or 4 days of constipation, poor sleep and terrible foginess. The more carbohidrates I eat, the more chills I get. The more sugar I take, the more emotional changes I suffer, the more fat I take, the more times I wake up in the night to use the wc… and the list goes on!!!

Do you want to stop having leg cramps? avoid refined flour… and there´s much more about at what time we eat what… I take a baby with a inmature inmunological and neurological systems for examples… one extra hour without sleep and you have a cranky baby next day…

Ok, I hope these simple arguments and observaciones help somehow.

Jenny November 28, 2012 at 6:26 am
MARGARITA COLOMBO

Antivirals are an extra help for our body for controlling viruses, like antifungals and antibiotics, but they also have downsides, like killing our friendly bacteria in the gut, making us more constipated or the contrary, etc.

I'd be interested the evidence for antivirals killing gut bacteria. Do you have any references, please?

Jenny

Cort November 28, 2012 at 9:19 am

I wanted to say in response to a comment that when I stated that Montoya and Kogelnik are digging through results to find immune markers…I think they're just doing a variety of immune and probably other tests and then seeing that improves as their patients…(they are getting substantial improvement in some patients). Then they can design a study to test out whether they're correct…

Cort November 28, 2012 at 9:21 am

I am trying to get in touch with Montoya by the way and see if we can find out what he's doing….Stanford is going to be a 'co-sponsor' of the 2014 IACFS/ME Conference – which is encouraging…The Bay area is a hotbed of medical research – having the conference there will be really intriguing..and its a beautiful area as well. Back to my old stomping grounds in the Bay area…:)

Enid November 28, 2012 at 9:23 am

Great work Cort – many thanks.

Cort November 28, 2012 at 12:50 pm

Love your tag. I hope that

'Sumer is icumen in'

- for sure…I think it could….:)

Enid

Great work Cort – many thanks.

alice November 28, 2012 at 1:14 pm
Jenny

I'd be interested the evidence for antivirals killing gut bacteria. Do you have any references, please?

Jenny

Yes, I really need to know this as I have developed lymphocyctic colitis. I cannot say for sure that antivirals have caused (or contributed to ) this, but if there is a reference then I could talk to my doctor about it. Thanks.

alice

MARGARITA COLOMBO November 30, 2012 at 10:34 pm
Jenny
MARGARITA COLOMBO

Antivirals are an extra help for our body for controlling viruses, like antifungals and antibiotics, but they also have downsides, like killing our friendly bacteria in the gut, making us more constipated or the contrary, etc.

I'd be interested the evidence for antivirals killing gut bacteria. Do you have any references, please?

Jenny

No, antivirals don´t kill bacteria directly, but anything altering the gut balance disrupts it, common secondary effects of antiviral drugs are diarrea. As I said, if I were to go on a medical protol I would go for Montoya´s one with no doubt, in fact I have had aciclovir many times in my life when I have needed it and has helped me, but I also do all I can for taking care of my gut. Taking probiotics is one thing that helped me a lot, but my diet was the more important thing I did. Basically I reduced carbs and went for unrefined ones, eating sparragus every day helped me too, and so on. I am sorry if I wasn´t clear.

Cort December 1, 2012 at 10:13 am
MARGARITA COLOMBO

No, antivirals don´t kill bacteria directly, but anything altering the gut balance disrupts it, common secondary effects of antiviral drugs are diarrea. As I said, if I were to go on a medical protol I would go for Montoya´s one with no doubt, in fact I have had aciclovir many times in my life when I have needed it and has helped me, but I also do all I can for taking care of my gut. Taking probiotics is one thing that helped me a lot, but my diet was the more important thing I did. Basically I reduced carbs and went for unrefined ones, eating sparragus every day helped me too, and so on. I am sorry if I wasn´t clear.

Hey Margarita…how much better did you get by working on your gut? On a scale of one to ten on your overall energy level….what change was there?

MARGARITA COLOMBO December 1, 2012 at 1:52 pm

I went from a 2-3 to a 6-7 in daily routines, I was able to go to classes twice a week, doing homeworks, and take care of little house chores, but exercise was the big change, I went from 0 to 7-8. Specially I noticed I had a very good aerobic capicity, curious things happened to me that NEVER in my life happened before. For example one day I had run about 2 kms and was about to start the 3rth leap when I saw an old fríend far ahead, I accelerated my pace to reach her, she was preparing herself for a marathon, we started runing togeher at her pace (much faster than mine) and at the end I acomplished a 5 kms run that day. I sometimes ran 5 or 6 kms. My body was NEVER IN PAIN or anything, in fact about 5 years ago I dont´have or use any medicine for aches or pain, I have had some specially last year, but for about 3 years I never had any pain. My phisical strenght was excelent, but as I said my sleep was poor and hence my cognitive functions were severly bad; I just don´t know if they were worst than before the diet and exercise.
Cort believe me: I was HAPPY while runing or swiming, and the general feeling I could describe was: I FELT THAT I HAD NO BODY, IT NEVER ACHED, I NEVER HAD TO CARRY IT! never had a cramp, never fatigued, nothing of bizarre symptoms at ALL.
I think that if we work in having controlled fungus and bacteria, virus stay dormant. Remember I have herpes 2 that bothered me for 15 years, chronic and severe. After runing that much, swiming, etc., I never had a problem with it, that´s what amazed me the must.

Something important is that during that time, I didn´t eat anything sweet, not even fruit. That healed my gut, but now I see i didn´t have enough glucose for my brain to work properly… so it seems like if I had to choose between phisical or mental well being… or not… that´s what I am triying to figure out these days. I making some research in Ayurveda and other sources. I am not sticking to any diet exactly, but doing my own tests.

The secret to be able to refrain from eating some food is to OBSERVE YOUR BODY´S AND YOUR MIND´S REACTION, wathc yoursel internally. For example, when you leave refined sugar, your anxiety lowers tremendously, you never have ups or down, etc.

I hope this helps you, and as I said, as soon as I figure out more, I will post it. Actually I started just today with new ideas about carbs etc., for example:for those of you who suffer from diarrea, I would try eating the carbohidrates you use to eat only in the night. Since I had my stomach infection last year I have had my bowels kind of more sensitive, and I have noticed that carbs make me tired and sleppy (sound logic since they help us produce seratonin and make us relax).

Ok, good luck!

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