A rough sketch of the NIH’s Clinical Center study for chronic fatigue syndrome (ME/CFS) has been posted. The good news about the study is that when Francis Collins said they were serious about ME/CFS he apparently wasn’t kidding. This looks to be the most comprehensive study ever done on chronic fatigue syndrome.
There’s also a bit of weirdness in the study which will make it more difficult for some to fully embrace. That’s unfortunate, because aside from that, all the indications to this point demonstrate that this is just the type of effort that we’ve been waiting for.
The Good
Post-Infectious Illness – The NIH’s focus on post-infectious illness; i.e. those whose disease was triggered by an infection, selects out what is probably the most important subset in this illness. Plus the researcher leading the study, Avindra Nath, is an expert in the central nervous system infections. The NIH got its priorities in this area right.
The Tests
The NIH will be throwing the veritable kitchen sink at the participants.
Two Day Exercise Tests – The specific kind of exercise testing that will be done was not clarified, but the fact that the NIH is going with a two day exercise test could have profound ramifications for this field.
A two-day exercise study gets central billing in the NIH’s study
It will be very important that the tests are done correctly, but if they are and the results are positive they could and should be a game changer. Staci Stevens, Betsy Keller and other exercise physiologists have stated that the drops in energy output seen in a significant number of ME/CFS patients have not been seen in any disease before. In fact they’re so unusual that they have to be seen to be believed.
One Canadian group reportedly visited Staci’s lab last year as skeptics and left agog at the results. If the results from the two-day exercise tests are positive it’s hard to see how the exercise study alone in this highly visible study won’t transform this field.
These tests, of course, are hard on patients and they must be done correctly. Staci Stevens and the Workwell Group know how to do these tests as safely as possible and have developed standardized protocols (the Stevens Protocol). Hopefully the NIH will bring in members of the Workwell Group and/or Betsy Keller to make sure the tests are done as safely as possible and according to protocol. This is an opportunity not to be missed.
Other Tests
- Autonomic Nervous System – sweating and breathing, being upright (apparently tilt table), blood pressure, and heart rate.
- Cortisol (presumably) – saliva test
- Cognition
- Heart monitoring
- Breath tests overnight – (small intestinal bacterial overgrowth?)
- Transcranial magnetic stimulation
- Functional MRI – the participants will do thinking AND exercise tasks in the MRI
- Spinal Tap
- Microbiome – gut, saliva and skin
- Blood Testing – the blood tests weren’t listed but given the comprehensiveness of the rest of this study one imagine many blood tests will be done
The Bad – Little Outside Participation
It’s hard to imagine that anyone (outside of the CDC) would have signed off on the criteria used to select patients (see below) and it doesn’t appear that any ME/CFS experts have been consulted. When that happens you can run into some problems – which this study has.
The Weird
Avindra Nath and the Clinical Center team have done something no one outside the CDC has done in the past ten plus years: they’re going to use the Empirical or as they call it “The Reeves Criteria” of 2005 to help define patients. That was kind of a jaw-dropper.
The Reeves criteria – where the heck did that come from?
The ME/CFS research community rejected it, the IOM poo-pooed it, and Lenny Jason tore it to pieces and the NIH resurrected it. It’s just the weirdest thing. After putting together what looks like a study everyone can embrace, the NIH somehow happened to pick the one thing guaranteed to drive the ME/CFS community nuts – they’re going with the Empirical definition.
Reeve’s plan with the definition seemed like a good one at the time. He would bring ME/CFS into the modern age by using questionnaires like the SF-36, Multidimensional Fatigue Inventory (MFI) and the CDC’s symptom severity list to quantify the symptoms in it.
The Empirical definition, however, has been suspect ever since Dr. Reeves invited ME/CFS experts to the CDC to prepare the ground for a new definition, and then disappeared with a small team to create the criteria for it (Ooops).
The plan ran into two major roadblocks. First, as Reeves was trying upgrade the ME/CFS definition using standardized quantitative assessments, the rest of the ME/CFS community was coalescing around highlighting post-exertional malaise. Second, some of Reeves criteria were so loose as to defy credibility. Reeves, for instance, set the functional criteria in the SF-36 needed to qualify for ME/CFS, at just 75% of norms – far above that typically found in other, less functionally disabling diseases such as asthma.
When a CDC study using the new criteria bumped prevalence up fourfold, it was clear something was wrong. Jason’s demonstration that criteria could possibly allow significant number of people with depression as having ME/CFS into studies, hammered another nail in the criteria’s coffin.
Why Reeves never went back to the drawing board to retweak the criteria, only he knows. Eleven years later, though, his criteria has never to my knowledge been used by non- CDC researchers – until now.
Not Garbage In – Garbage Out
Of course the use of the Empirical Definition, i..e the “Reeves criteria” is causing great dismay. Garbage in, they say, garbage out some say. Calls have been made for the study to be boycotted and petitions have begun. I think the criteria should be replaced but I don’t think the criteria is the study killer some are making it out to be. In fact, my guess is that this study is structured in such a way as to make the criteria mostly a non-issue.
The main worry about the Reeves criteria was the possibility that people with depression but not ME/CFS could be mistakenly end up in ME/CFS research studies. That issue is most concerning in randomized sampling studies that pluck their participants out of the population at large. In those efforts the criteria is the only filter.
The filters should allow the right patients into the study
In other studies which get their participants from doctors office or by asking for people with ME/CFS to enroll, filters are already in place to weed those people out. The Clinical Center study comes with three filters that I believe will make it very hard for anyone who doesn’t have ME/CFS to get into this study.
Filter #1 – ME/CFS Diagnosis – The study is calling for people diagnosed with ME/CFS to apply. The depression issue is only an issue if people with depression get misdiagnosed as having ME/CFS and then apply to be in the study. Most of us know from personal experience, however, that doctors are prone to misdiagnose ME/CFS as having depression.
The reverse – that people with depression are getting misdiagnosed as having ME/CFS is surely very rare. Most doctors simply don’t know enough about ME/CFS to make that mistake. When they see a patient suffering from mood problems, fatigue, etc. they’re going to diagnose them with depression – not the reverse. A horde of depressed patients masquerading as ME/CFS patients just isn’t out there.
Filter #2: Infectious Onset – the NIH requires doctor certified infectious onset be required to be in the study. The fact that an infection started off the disease has to be in the doctors records. Infectious onset is common in ME/CFS but the percentage of people with depression who’s medical file states that their depression can be traced back to an infection is surely miniscule.
Filter #3: The Reeves Criteria – Jason’s study suggests that the Reeves criteria could misdiagnose 38% of people with depression as having ME/CFS. That’s not good news but it means hat the criteria rejects over 60% of depressed patients. So even if someone with depression but not ME/CFS somehow got past the first two filters they would probably get knocked out by the last one.
These three filters appear to make it almost impossible for someone with depression but not ME/CFS to get into this study. First you would have to get misdiagnosed as having ME/CFS, then you’d have an infectious onset to your depression documented in your medical records, and then you have to make it past the criteria. For those reasons I don’t see the Reeves criteria being a particular problem in this study.
Postexertional malaise (PEM) – the Reeves criteria does not require PEM. Does that mean people without PEM are going to show up in this study? Because PEM is very common in the ME/CFS population, people who have already been diagnosed with this disease are very, very likely to have it. Plus I would imagine that almost everyone with infection triggered ME/CFS experiences PEM. This study should be loaded with patients with PEM.
Using the Canadian Consensus Criteria
Still, I think we should push for use of the Canadian Consensus Criteria (CCC). Why? The CCC focuses on post-exertional malaise and the IOM report – which started all of this – endorsed a definition that focuses on PEM. CFSAC recommended it be used and it (and the Fukuda Definition) were required during XMRV testing.
The CCC reflects the experience of the ME/CFS community; the Reeves Criteria does not. The CCC was put together by a team of doctors and researchers with vast experience with this disease; the Reeves Criteria was put together by a smaller group with less experience. The CCC has its problems but its largely been accepted by the researchers and doctors associated with the disease. The Reeves Criteria has been a total flop.
The CCC, then, is the natural choice for this study. You don’t lose anything that I can tell of by using it. If you do use it everyone can rest easy and will accept the results. That’s important. Plus, the NIH earns some trust, is acknowledged for their flexibility, and an excellent study moves forward without a pall hanging over it.
Update!
Bob and Courtney Miller have a way of getting answers fast- and they got some good ones:
Robert and I had a well-timed chance to discuss with NINDS some questions about the protocol that was posted this weekend for the NIH Clinical Center study. There will be additional information posted on a website for patients and the community which may take a week to be live, they said.
We asked questions about the criteria for enrollment, reference to Reeves criteria in the protocol, role of ME/CFS experts and the choice of control groups. According to the principal investigator of the study:
Enrollees will meet all definitions for ME/CFS, including Canadian Consensus Criteria, IOM, Fukuda and Reeves, in addition to post-infectious onset.
Post-exertional malaise (PEM) is a criteria, and will be specifically studied with extensive testing before and after exercise challenge.
The SF-36 criteria to measure functional impairment stated in the protocol online is inverted mistakenly. “Greater than” is meant to be “less than” in the SF-36 measures.
Dr. Ian Lipkin of Columbia University’s Center for Infection and Immunity has been advising the investigators on the study design and protocol.
Expert clinicians will be used in patient selection.
Control groups: Asymptomatic Lyme was chosen to contrast post-infectious ME/CFS patients to patients who recovered from an infection. Functional Movement Disorder was chosen to contrast post-infectious ME/CFS patients with a very well-studied group of patients with clear psychological illness with neurological presentation.
They seek to have 40 PI-ME/CFS patients, and they will study them longitudinally, hoping to learn how and whether the disease changes over time.
Testing will be extensive.
We are very excited to know that the NIH intramural study is moving forward, and that it will deeply study patients with infectious onset against a battery of biological tests. We are reassured by these answers, and eager to have this kind of data to move our disease toward discovery.
Control Groups
The study will also compare ME/CFS patients people with Lyme disease without fatigue (that must be a typo, and not the first one) and people with functional disorders which respond to psychiatric treatment. These extra control groups bear the mark of other researchers wanting in, and getting into this Clinical Center trial.
Lyme disease patients would be an excellent control group, and I’m not worried about the functional disorders control group. ME/CFS first had to “prove itself” against depression and it did and I have no doubt that it will do the same against functional disorders. (Psychiatric treatments, as we know, are no panacea). Showing itself to be distinct from functional disorders that will simply provide further validation for ME/CFS.
Questions
The outlines of the study given were sketchy and questions are pouring into the NIH about this study from The Solve ME/CFS Initiative and advocates. We don’t know why they chose to use the Reeves criteria, how many ME/CFS patients will be involved, what blood tests they are going to do, what tests are going to be given before and after the exercise tests, etc.
Vicky Whittemore Holets has agreed to answer them as quickly as possible.
The Best Study Possible
It’s critical that the study be done correctly. Standard cognitive tests don’t show up all the abnormalities found in ME/CFS. Nor do some kinds of exercise tests. Herpesvirus tests require different procedures than other viral tests. In some ways ME/CFS is different.
Plus much of what will be hot in the next year or so hasn’t made it to publication yet. How about querying our top researchers about unpublished data that could inform this study? What does their intuition tell them about where to search for answers?
The End ME/CFS Scientific Board with its clutch of Nobel Prize winners, for instance, is having wide ranging discussions about what’s next for ME/CFS. They’re laying out a pathway for discovery. There’s simply no way that the NIH group – as talented as they are – can match the experience that groups like this have. When you’re casting a broad net like the NIH is, you want it to land in the most fertile waters possible.
Conclusion
The use of the Reeves criteria introduces a bit of weirdness into this study but the key thing for me is that the study indicates that Francis Collins was indeed serious when he made his promise to move aggressively on ME/CFS. The NIH is not going through the motions here; they’re employing one of their top researchers to lead the deepest and most comprehensive study of ME/CFS than has been done.
The future looks a little brighter with a study like this underway.
The study will make waves in the way that others have not. A major issue for this field has been small studies done by less well known researchers landing in less-respected journals. Even when the results are positive they simply don’t get the impact they should.
That’s clearly not going to happen with this study. The results from a study of this size lead by a researcher of Nath’s ilk will surely land in a prestigious journal. Any positive results will lay the foundation for future studies. The exercise study results alone could transform this field.
If this kind of study portends what our future with the NIH is like we have something to look forward to. The new era is off to a good start.
Where and when will these trials/studies be held?
Neena241@optonline.net
They’ll be held in the Clinical Center on the NIH campus near or in Baltimore Md, I believe. Not sure about the date but it’s reportedly in the next couple of months.
As usual, you did a great job of summing up and analyzing the NIH study. I agree that the criteria should be replaced. (Didn’t they read the IOH report?)
However, I don’t think it does much good to threaten boycotts, etc. We have reason to be angry and bitter about a lot of things, but we should do what we can to support good-faith research efforts.
I’m hearing some good rumors about the NIH’s willingness to be flexible on the criteria. We shall see!
It took me a long time to understand PEM, I just never made the connection between my bad days and what I had done preceding them until I became severe.
I think an infectious onset is possibly more important.
Thanks for the wonderful summary Cort! What I love about your site is that I feel like I can take my eye off the ‘ball’ at times (or this big-picture part of it, anyway) knowing that you will let us all know if anything truly important comes up in the field. (I often have my own hands full following up on the leads that you provide…at the moment I’m making my way through the Heal Your Gut Summit lectures, and making another radical series of changes to the way I eat and prepare food.) So, it’s such a wonderful service that you provide, really!
This NIH study sounds very hopeful. Those pre-study filters seem like the key to seeing it primarily as a positive step. So glad that you took the time to explain that. Hope for us all that they turn up a ton of good data!
Hope you are well! Martha
Good luck with that Martha! Let us know how it goes. You never know 🙂
Thanks Cort! Gonna need it! Yes, I’ll be sure to let you know if fermented vegetables and bone broth turn out to be my miracle cure. Just trying to wrap my head around becoming a modern day homesteader…on top of everything else. But, yes, you never do know….
Be sure to look into histamine and tyramine intolerances when you change your diet. The new foods could make you worse; they did for me. It was a huge missing dietary piece for me to understand histamine and tyramine intolerances. I could eat chicken and rice and vegetables, but once I made a soup out of those same ingredients, I’d usually be sick and have a migraine. Sometimes I could eat tomatoes, other times they’d make me sick and I’d have a migraine. The same with the teas I drank. Fish always made me sick and gave me a migraine. Soups, fermented foods and many other foods were a problem with histamine and tyramine being the common denominators. It can be very confusing because the offending food may not make you worse every time you eat it; you may even eat it for long periods of time (years) and not suspect it. It may be the accumulation of histamine and/or tyramine containing foods eaten at one time that causes the problem.
Good luck Martha and I hope you find things that make you feel better.
Thanks for the good wishes, and for the heads up about histamine Laurie! Isn’t that always the way with this beast?…every source of possible hope comes with a counterpoint of possible harm.
I read a bit about histamine intolerance some years ago, but am glad to have the reminder of it. It is super confusing because one of the top cited reasons for histamine intolerance is a damaged gut and associated imbalance in gut bacteria (which would surely be true in my case). But many of the foods that are most commonly suggested to help heal the gut (especially fermented foods) are the exact same as those on the list of what NOT to eat for histamine intolerance (as your post suggested). Oh dear.
Well, all I can do is try. I have had a lot of luck adding probiotics already, and this diet is just a more refined version of how I have already been eating. But I have also come to think of my migraines as histamine headaches. So if things go south I will try the exact opposite diet next! Thanks again for the suggestion! Martha
I did not have any infectious agent trigger my cfs. Any idea how this will be adressed?
It will have to be in another study. I would note though that I didn’t have infectious onset either but then I read that infectious mononucleosis can manifest itself in a gradual way with fatigue, muscle pain and stuff like that – but not your usual flu-like symptoms – so I don’t know about myself now.
Thank you for the reply. I guess any study is good for cfs!
I had mono 3x – at 17, 25, and 48. The last led to ME/CFS. Open Medicine Institute considers me a classic EBV viral onset.
I’m in the same boat — my CFS seems to have started in the wake of an autoimmune disease and/or its treatment, not any virus that I can recall. In some ways it’s a shame, because I live in DC, have severe CFS, and would happily have volunteered. But they’re probably wise to keep it to a single potential disease subset in terms of keeping the data simple. (Not sure how that fits their choice of what sounds like a broad definition, but requiring doctor’s virus records should probably counteract that.)
I think so. The study is also limited to people with ME/CFS for less than five years. I think that’s just the group they have the best chance of getting good results for. After that gets some traction they can move on.
This study sounds excellent. I wish they would use Canadian instead of Reeves, but as you pointed out well in the article, that’s likely to be more of a theoretical issue than a pragmatic one.
I don’t think the control group of people with Lyme disease *without* fatigue is a typo. I think what they’re trying to determine is a difference between a person who has had a known infectious disease but did not develop ME/CFS and the study group. It’s absolutely fantastic, in my view, that they are including people with functional somatic disorders that are responding to treatment. Finally, definitive proof on the way that ME/CFS is NOT a psychiatric disorder (and I have no doubt, if the study is done honestly, that will be proved. No one with only a psych disorder and not ME/CFS is going to have PEM).
I’m afraid I’m just as dismayed by having a researcher with no previous experience with CFS as with the criteria! I know you’ve talked about being excited about this fellow before, but there’s nothing in his CV that mentions any prior interest in our disease. I’d much rather have seen Ian Lipkin head up the research with this guy doing the retroviral pathophysiology of neurological infections as part of the research. His CV pales by comparison to Lipkin’s as far as infectious disease is concerned!
How in blazes did the Reeves criteria get resurrected? I think it is a bureaucratic move – one set of bureaucrats against another.
But – back in the late 1990s, I once asked the Surgeon-General how CDC could be saying 500,000 and NIH could be saying 20,000. He was furious – he said NIH had to adhere to CDC on definitions and demography. SO, the problem could be CDC.
We have to fight it, because the Reeves questionnaires roll everything backwards. In the article where he introduced the questionnaires, he explicitly referenced Wessely’s questionnaires. [For those who do not know, Wessely is the leader of a group of psychiatrists in England who argue that we have “false illness beliefs” and only look sick because we are “deconditioned” – so CBT (cognitive behavior therapy) targeted at teaching us we really aren’t sick plus GET (graded exercise) to make us get into shape is all that is needed to fix us. To the contrary – Those two treatments remain on CDC’s website today. That version of CBT is cruel, and GET is actually dangerous to patients with PEM. ]
Using the Reeves questionnaires, CDC came up with a prevalence rate of 4-6 million – as opposed to Lenny Jason’s estimate, which would be around 1 million today. Who were the extra patients? Most likely those with primary mood disorders. Is it a coincidence that the 4-6 million figure is precisely what you would get if you applied Wessely’s estimates to the US?
Five years ago I wrote a blog post deconstructing the 2-day Wichita hospital stay which Reeves claimed “proved” that his questionnaires accurately diagnosed CFS. I really thought it was a dead issue! FWIW, here’s the post:
http://slightlyalive.blogspot.com/2010/02/cdc-research-on-cfs-open-deception.html
I truly believe it is the US version of the UK’s PACE scandal, and it would be a travesty of justice if it were to be resurrected by NIH.
They are saying now that the patients in the CFS group will meet ALL the various criteria. That should cover it. That’s what the End ME/CFS project is doing too.
I also want to thank you, Cort, for providing a place where we can discuss this.
It depends entirely on the intentions of the researchers. Some research will be done with the intention of supporting the psychosocial version of ME/CFS, and the use of Reeves (which clearly was a response to Strauss’s wish to keep the focus on fatigue as a general symptom so as to ‘evaporate’ the idea of a specific disease entity. The use of Reeves suggests that this intention may still be influential (why are they using a researcher who has shown no previous interest in ME/CFS) However, on the bright side, I think they wanted the IOM to do that, and it didn’t. We live in hope!
When you include ‘herpes virus,’ does that mean Hep A, B, C, Z–whatever? When I was told my mono was ‘mono with infectious hepatitis,’ my doctor said it was no big deal, infectious hepatitis was ‘just Hep A.’ Is a particular strain related to ME/CFS and how do they know–or is this part of the study?
Herpes and hepatitis viruses are different virus families.
Herpes are human herpes viruses (HHV’s)-
HHV1 and 2- oral and genital herpes
HHV3- chicken pox
HHV4- Epstien Barr virus- causes infectious mononucleosis
HHV5- cytomegalovirus- also a kind of mono
HHV6- some other childhood disease
HHV7- Not sure what disease this causes
HHV8- Not sure what disease this causes except for Kaposi sarcoma in AIDS
Hepatitis viruses are-
Hep A, which you recover from but causes a temporary jaundice type disease,
Hep B, which I think you have for life and causes liver damage
Hep C, which you also have for life and also causes liver damage
I wish they would test for herpes viruses, but in a gradual onset cohort. I started becoming ill in the late 90’s with a gradual onset and progressive disease course. I contracted genital herpes in Fall of ’03 and in Spring of ’04 I had my first outbreak. Within three weeks of the outbreak I plummeted from 40-50% functioning to 10-15% functioning where I’ve continued to get progressively worse ever since. Seems too fishy to be a coincidence to me, I’m thinking I might have a genetic inability to control herpes viruses or something like that. My thyroid antibodies are through the roof too but TSH is controllable with a tiny bit of thyroid hormone a couple times a month. Never tried antivirals though.
TSH is a pituitary hormone and not a good indicator of thyroid gland functioning. Free T4, Free T3, Reverse T3, and as you mentioned thyroid antibodies will tell you a lot more than TSH about how your thyroid is functioning and what thyroid hormone is getting into your cells.
Sally, EBV can cause hepatitis. Hepatitis just means inflammation of the liver. There are many causes.( check PubMed “Epstein Barr induced hepatitis: An important cause of cholestasis. Shauket et al. ) EBV is also known to cause thyroiditis and has a predilection for the autonomic nervous system. Plus, so many other things. A really horrible life form. Hah, is it really even alive?
How do you get into these studies? I had the infectious onset 27 years ago.
How are they going to get people to spend their spoons so recklessly? Keep them there? Let them stay over night? How will they pick their subjects to ‘study’ when most of use have the energy for so little at a time?
Those are important questions.
You would not actually qualify Alicia as the study requires a patient to have been sick for less than 5 years to be in the study. In answer to your other questions they are planning to keep patients in the hospital for a week to do several of the tests. And this leads to your third question which was also a concern of mine, that this study will only select the healthiest of ME/CFS patients. I am pretty functional (I can’t work but can go out of the house every day, care for my self and walk for a few minutes) and I would never participate in a study like this due the risk of a severe and long lasting increase in symptoms. The study would also seem to select geographically as patients who are well enough to travel to the study location for a week or more are likely to be healthier. That said overall it is a very comprehensive and thorough study and should produce some interesting results.
With all due respect Cort, their process of ‘informing’ the public / patients of the study leaves them with little credibility. Typos, non-consulting with patient groups, erroneous public release of study, wtf with Reeves, and on and on. It is self-evident they don’t know what they are doing on every level. They will need to step up the quality of their game before I will pay them any heed. Not holding my breath.
“A rough sketch of the NIH’s Clinical Center study for chronic fatigue syndrome (ME/CFS) has been posted.”
Does anyone have a link to this page? I can’t seem to find it. Thank you.
Sorry – http://clinicalstudies.info.nih.gov/cgi/wais/bold032001.pl?A_16-N-0058.html@chronic@fatigue@syndrome@@
I hope they consider looking also at non-invasive biomarkers like nitric oxide, that is a very cheap 2 minute test. Cytokine storms may lead to more NO = Nitric oxide, that could dilate blood vessels and perhaps contribute to ME related POTS. $10 test with handheld meter.
Good news is that Open Medicine is already starting a donor funded biomarker study on 20 of the most severe M.E. patients in SF Bay area. These people are so ill, they cannot get to the doctor office, to OMF will travel to them, so it will luckily give a second opinion from a separate population, which is key since different locations may tend to have different triggers and perhaps different biochemistries. See End-MECFS.org for updates.
If Obama can throw $1.8B for Zika that has affected a handful in US, and Billion for Ebola that has affected few, $3B R&D for AIDS per year, he and Feds, Congress should be able to fund $250M/year for R&D to cure M.E.
NIH is moving forward and finally also CDC, with free ME/CFS Grand Rounds webinar 1 pm EST Feb 16th. Please try to watch this, apply for CME credit, and ask every MD and medical healthcare professional to watch this. Showing high interest will also be a vote for more focus on curing ME/CFS. No signup needed, just go to: http://www.cdc.gov/cdcgrandrounds/archives/2016/february2016.htm
I think our worst fears can now be relieved.
http://www.meaction.net/2016/02/09/positive-answers-to-initial-questions-re-nih-clinical-center-protocol/
Someone should throw those stats out there….its just absolutely mind blowing how they handle this one. We are truly the forgotten plagued.
The control groups are my main concern.
Recovered Lyme disease controls: While the concept of using “recovered” Lyme patients sounds interesting, I’d have some concerns about the testing used to establish Lyme disease, and the robustness and duration/ sustainability of recovery, and probably more if I thought about it. I’m all for the study of Lyme disease, it clearly needs more attention, but it’s not a control that would spring to mind in an ideal study.
Functional Movement Disorders – psychogenic. Why are they an excellent control group? How well studied are they? What do we know about the studies done on this group, and what would make them suitable controls? I think it would be very interesting to look at robust study results on this group. Without knowing more, I’d be concerned that they may not be a good control, unless there is already a good baseline on them for the types of testing to be done in this study. There could very well be disordered pathways that might be studied here, that have not previously been studied in this group, to exclude potential non-psychogenic factors.
Here we are, after PACE and the lack of a true control group, and poor comparison groups, have been roundly criticized by critics beyond the usual advocacy community. We don’t want NIH muddying the waters for posterity.
I’m actually grateful about the “erroneous” posting, because it looks as if we have real reason to be concerned about how this study is being designed. It almost sounds like they picked a bunch of “controversial” diagnoses and lumped them together. I think each is deserving, but not necessarily in a study purportedly about ME / CFS.
I’d also like to know more about why there are control groups here. If it’s a data mining exercise, they can do that independently for each group, and it should NOT get all lumped into ME – CFS research. People can always look at separate study results for each group if they want to draw up hypotheses for future study. However, if they have null hypotheses being tested by these controls, show me the hypotheses, please, and explain the rationale for “control” groups.
So, please do not count me satisfied in any way with what we know so far.
Those are excellent control groups. By using people who have functional somatic illnesses that have responded to conventional psychiatric treatment, we can prove that ME/CFS is not a functional somatic illness that would respond to conventional psychiatric treatment. The functional somatic illness group does not experience PEM.
By using Lyme patients who do not have fatigue, the research can establish that ME/CFS is its own disorder distinct from Lyme. Someone who had Lyme who does not have fatigue is also not going to have PEM. That will prevent doctors from grouping people who have ME/CFS in with Lyme patients and saying they “just have Lyme.”
This research is not studying functional somatic illness or Lyme disease and “lumping them in” with ME/CFS. It’s studying ME/CFS and using functional disease and Lyme as sensible and intelligent controls.
this looked pretty promising until the last post said they would only study 40 patients. I would participate in an exercise test, although it would wipe me out for months, if done in the UK. I’d offer to fly to America but I’m not sure I’d be able to fly back again afterwards. However I cant really trace my illness to a specific infection.
The researchers need to recognise they aren’t getting the sickest people, there is a study going ahead in Newcastle, UK on some of them but obviously it wont involve exercise tests.
I think this is very bad research. Starting with the Reeves criteria. It totally makes the exercise test biased. And only the 2 day exercise test could provide a biomarker for objective invalidation in ME patiënts, it is unique! We know this for decades. I don’t see a PET scan tudy like Japan. So nothing will be changed by this research, nothing! I am very disapointed as Always. Are Scientists blind or stupid?
How can a person volunteer for this study?
Several points of interest and one correction-
1. The saliva test- If they are going to be testing saliva for cortisol, they should probably be testing multiple times a day to test for altered diurnal cortisol rhythms and not just a one time test for high/low cortisol.
2. The fMRI- From what little I’ve heard about fMRI, it’s kind of a Wild West in terms of fundamental validity, clinical relevance, etc. Basically, they still haven’t even figured out the basics of anything regarding this test. IMO, this is why it’s so popular with the psychobabble crowd- you can get it to tell you whatever you want due to the sheer amount of data points, what points to keep/delete, etc. With the numerous reports of unidentified bright objects (aka UBO’s) in brain scans of ME/CFS patients using traditional MRI, it’s hard to see why they don’t just use that in place of, or at least alongside, the fMRI. Also, why no SPECT/PET scans? Those are some validated, objective as hell tests that have also been reported in the past as being abnormal in ME/CFS patients.
3. “Plus much of what will be hot in the next year or so hasn’t made it to publication yet. How about querying our top researchers about unpublished data that could inform this study?
That sounds like a crackerjack idea.
Correction-
“Second, some of Reeves criteria were so loose as to defy credibility. Reeves, for instance, set the functional criteria in the SF-36 needed to qualify for ME/CFS at just 75% of norms – far above that typically found in other, less functionally disabling disease such as asthma.”
– I don’t think it was 75% of norms, it was below the 25% quartile, ie a SF-36 score of 70. Still a mind blower of a decision though.
🙂 I think the consensus around cortisol is that early morning saliva cortisol is what stands out. Hopefully they’ll do it over the entire day thought.
Thanks for clarifying the SF-36 – at least it was a bit lower 🙂
Good idea on the SPECT- check out the next blog!
If the saliva test is the ASI (Adrenal Stress Index) test, it covers 4 tests in a day for cortisol plus some other related tests included, such as DHEA. This is the kind of test my doctor had me take back in 1999 in order to find out how my levels of cortisol over the course of a long day compared to those of normal people. My doctor felt it was the best test to determine whether or not cortisol was actually available to my body.
I’m curious about the two-day exercise test that the Workwell Group performed. Your article states “that the drops in energy output seen in a significant number of ME/CFS patients have not been seen in any disease before. In fact they’re so unusual that they have to be seen to be believed.” What exactly did they measure? Do they have any clue what caused the drop in energy? Thanks Cort.
Hi Gail,
I have done the 2 day cardiopulmonary exercise test at Workwell Foundation. You can look up CPET to see what it measures, but I will do my best to summarize it here. one rides an exercise bike with a mask on to measure oxygen use and carbon dioxide produced. You have electrodes on to measure heart function and blood pressure is taken periodically. You do the same test again 24 hours later.
-The maximum volume of oxygen your body uses to produce energy is measured. Mine dropped 19% which is not normal.
-They look at the ratio of oxygen used to carbon dioxide produced to be sure you have exerted yourself enough for the test. You can’t fake the results.
-Workload is measured when you are working your hardest to pedal and when you reach your anaerobic threshold. One the second day, I reached my anaerobic threshold at 18% less work. (Your anaerobic energy system is designed for short term, intense energy output-think 50yd/m dash. It is thought that people with ME/CFS are living much of their lives using anaerobic energy.)
-Heart rate and blood pressure responses to exercise are measured and compared to predicted values for someone who is healthy.
-They also measure lung function by putting a tube into your mouth and having you 1) breath as fast as you can and 2) breathing in as deeply as you can, then blowing it out as fast and hard as you can.
This is the first time I’ve seen in print the main expression of my experience with CFS. I’ve been diagnosed with venous insufficiency, but I experience CFS along with it which is not common. This “post-exertional malaise” fits my situation exactly. I would invite others to share their experience with me. After a few days of feeling well and probably overdoing it,e.g., I may swim a couple days, feeling really good, followed by a day I am feeling so very weak inwardly, as if my main organs have been drained of life-giving blood. I am only able to lay flat all day and night, sleeping through the night to be renewed. During the day I am lethargic, weak and sleepy, I cannot get up to do anything, other than fix a small meal. I have no brain power to read. I sleep on and off throughout the day until the following morning. I never know when this will occur so working a 40 hour week is impossible, and sometimes even so I must cancel an appointment, or lunch with a friend. I am so happy to hear about this study and would jump to be considered to be a client in it. So glad I have found you all. Suzanna
That’s PEM. To be honest Suzanna – your case, as distressful as it is, is pretty moderate compared to some others. Swimming and feel good is pretty much. It demonstrates how variability this is….It’s takes me much less to overdo it but I don’t think I relapse as bad as you do.
Thank you Cort for this detailed explanation of what is happening in the research world. I appreciate that our scientific research is not always objective, and that politics play a role. ( ha! The William Thompson CDC vaccine case!!! ) Just being hopeful that some meaningful results shake out of this. Glad that Ian Lipkin has/is having input. Wish someone would talk to Don Gilden, Dept. of Neurology, University of Colorado. He is recognized as a ‘Pioneer in Neurovirology.’ Received the 2007 award for individual achievement in Neurovirology – given by the International Society for Neurovirology.
Thought: Cort send him an email for an interview and opinion on all of this? I actually wrote to him 4 or 5 years ago concerning this mess ( CFS/ME ) and he kindly wrote back with a thoughtful response.
Question, Cort? The head shot boxes in the comments section cover the text of the comments. Is this happening to other people or is it just something wrong with my computer and how it is set up? Anyone else having this problem? Thanks, Esther
Yes Esther I have the same problem -can’t read info as head box covers it.
Darn, I thought we’d fixed this a month ago. Esther what browser are you using.
Cort. Awesome news!!! Which advocacy group do i need to contact with my thoughts and suggestions? Email, website?
Can the NIH be contacted directly with regard to this study to get patient input? Same Email Website?
I think this would be a great opportunity to get a Change.org petition going…..to be sent for refinement of a few of these components of the study?
I’ll have a blog up today. MEACtion is the place to go for advocacy.
I am a 57 year old male in north Dakota with severe cfs after 2 surgeries get exhausted when I stand up been to 50 doctors headaches dizzy and exhaustion don’t know what to do am on the guaifenisen protocol for fibro some better need help doctors don’t know what to do