NIH post-infectious CFS study

[Scarecrow]

Jason showed that flaw brought in a lot of depressed patients. And as @Bob pointed out, depressed patients are allowed in as long as they are stable (personally I have no problem with including depressed patients, so long as they have mecfs too).

Actually it was me that pointed this out, although it applies to all participants. I'm wondering if the number of depressed individuals will be higher in the PI-CFS and FMD groups than the healthy controls and successfully treated Lyme participants. Could this confound some of the tests?

 

[duncan]

@Scarecrow , where does it say the Lyme candidates need to have been successfully treated? In fact, what do you imagine they mean by an asymptomatic Lyme patient?

 

[Scarecrow]

@Scarecrow , where does it say the Lyme candidates need to have been successfully treated? In fact, what do you imagine they mean by an asymptomatic Lyme patient?

Here are the inclusion and exclusion criteria for the Lyme group:

Additional inclusion criteria for Documented Lyme Infection Asymptomatic group:
-Medical record documentation of fulfilling the probable or confirmed 2011 CDC Lyme Disease National Surveillance Case Definitions (http://wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2011/):

--Probable: A case of physician-diagnosed Lyme disease that meets laboratory criteria of evidence of infection (positive culture for B.burgdoferi, or two-tiered testing using criteria, or single-tier IgG immunoblot seropositivity using criteria, or CSF antibody positive for B.burgdoferi by Enzyme Immunoassay or Immunofluorescence Assay, when the titer is higher than it was in serum.
--Confirmed: A case of erythema migrans with a known exposure, or a case of erythema migrans with laboratory evidence of infection and without a known exposure, or a case with at least one late manifestation that has laboratory evidence of infection.

-Have received accepted antibiotic treatment for Lyme Disease greater than or equal to 6 months prior to enrollment but less than 5 years prior to enrollment documented in their medical records.

Additional exclusion criteria for Documented Lyme Infection Asymptomatic group:
-Clinical relevant fatigue as determined using the Multidimensional fatigue Inventory (MFI): score of > 8 on the general fatigue subscale or > 6 on the reduced activity subscale.
-Significant neurological disorder (e.g. neurodegenerative disorder, stroke, epilepsy).
Symptoms or diagnosis of Post-Lyme Disease syndrome

So the participants must have received antibiotic treatment to a documented Lyme infection, they must now by asymptomatic, i.e. have no symptoms of Lyme or post-Lyme disease syndrome.

Edited to add: I don't think the NIH used the phrase 'asymptomatic Lyme patient', they refer to the 'Documented Lyme Infection Asymptomatic group'.

 

[duncan]

Right. And yes, they don't say asymptomatic Lyme patient - but they DO say Lyme Infection Asymptomatic group - same difference to me.

They note "treated." They note asymptomatic. But they do not specify successfully treated or cured. Perhaps too fine a point, but I would direct you to the broad relapsing remitting nature of Borrelia. Or for a better comparison, babesia or malaria. I'm just finding it significant that a) Lyme is highlighted the way it is to begin with for an ME/CFS study, and b) they seem to me at least to be tip-toeing around the status of potential Lyme participants - if you deem them cured, if that is a requirement for inclusion, then say so.

 

[Scarecrow]

They note "treated." They note asymptomatic. But they do not specify successfully treated or cured. Perhaps too fine a point, but I would direct you to the broad relapsing remitting nature of Borrelia. Or for a better comparison, babesia or malaria. I'm just finding it significant that a) Lyme is highlighted the way it is to begin with for an ME/CFS study, and b) they seem to me at least to be tip-toeing around the status of potential Lyme participants - if you deem them cured, if that is a requirement, for inclusion, then say so.

You may well be right. It's certainly very careful language. In any case, I think the most significant word here is 'asymptomatic'. What they definitely don't want is anyone who is suspected to still have Lyme because of indicative symptoms. What else lies beneath, I could not say.

 

[Nielk]

MEadvocacy.org blog and petition.

http://www.meadvocacy.org/nih_clinical_study_a_case_of_continued_institutional_bias

 

[dancingstarheart]

This is another grab-bag diagnosis, a total waste of time. Unless ... they are hoping that they can sneak some of these patients in and find out what is really wrong with them.

I am concerned that they will say that ME patients were misdiagnosed functional movement disorder, than the other way around. They already believe the mind controls the brain to make changes during a fMRI for FMD/ somatoform disorder. Now the study would let them compare ME fMRI studies and say the cause is also psychogenic. Instead of admitting they were misdiagnosing those poor people with conversion/ somatoform disorder. See link for discussion on imaging to diagnose somatoform. (note following title was already in caps from article)

"CAN NEUROIMAGING HELP US TO UNDERSTAND AND CLASSIFY SOMATOFORM DISORDERS? A SYSTEMATIC AND CRITICAL REVIEW"
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044887/

 

[Forbin]

Jason showed that flaw brought in a lot of depressed patients. And as Bob pointed out, depressed patients are allowed in as long as they are stable (personally I have no problem with including depressed patients, so long as they have mecfs too).

This is serious concern, as Jason's 2009 study showed that the Reeves criteria misclassified 38% of the MDD patients in his study as having CFS.

Abstract
The Centers for Disease Control and Prevention (CDC) recently developed an empirical case definition that specifies criteria and instruments to diagnose chronic fatigue syndrome (CFS) in order to bring more methodological rigor to the current CFS case definition. The present study investigated this new definition with 27 participants with a diagnosis of CFS and 37 participants with a diagnosis of a Major Depressive Disorder. Participants completed questionnaires measuring disability, fatigue, and symptoms. Findings indicated that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using the new CDC definition. Given the CDC’s stature and respect in the scientific world, this new definition might be widely used by investigators and clinicians. This might result in the erroneous inclusion of people with primary psychiatric conditions in CFS samples, with detrimental consequences for the interpretation of epidemiologic, etiologic, and treatment efficacy findings for people with CFS. http://dps.sagepub.com/content/20/2/93.abstract

I'm sure it could be argued that the current NIH study's requirement of...

"A self-reported illness narrative of the development of persistent fatigue as the consequence of an acute infection"

...would, at least, narrow this down. It would seem a lot harder to find pure MDD patients (i.e., without CFS) who developed fatigue only in the wake of an acute infection. Still, it would be fairly ad hoc to rely on that combination to counter to the deficiencies of "Reeves."

 

[dancingstarheart]

You may well be right. It's certainly very careful language. In any case, I think the most significant word here is 'asymptomatic'. What they definitely don't want is anyone who is suspected to still have Lyme because of indicative symptoms. What else lies beneath, I could not say.

Specifically it was asymptomatic for fatigue symptoms. "had Lyme disease, were treated, and don t have fatigue symptoms"

So does this mean those post-treatment arthritic knee lyme patients are acceptable as long as they don't have fatigue?

The selection of this cohort does not make sense to me.

 

[dancingstarheart]

They forgot to mention where you live being an inclusion/exclusion factor.

I'm also perplexed by this exclusion criterion:
"History of head injury with loss of consciousness, or history of head injury with amnesia lasting greater than a few seconds".

As a schoolboy I used to play rugby at county level and was knocked unconscious several times. The last time it happened (thirty years ago now) I had amnesiac episodes for up to a year. I had several brain scans, which were "normal". My current ME/CFS symptoms started abruptly after an URT infection three years ago. Why on earth should my historic episodes of unconsciousness be an exclusion factor? Are they saying all my current flu-like symptoms etc. may be a result of some delayed and hitherto undetected neurological damage?

My guess is they do not want artifacts from old brain injuries interfering with their fMRI scans. Plus, multiple small concussions and also severe concussions have been shown to lead to dementia symptoms. So easier just to say no to all with that type of injury.

 

[Kati]

I received notification this morning of a 'storify' tweet gathering by NINDS.

https://storify.com/NINDSnews/chron...ign=website&utm_source=email&utm_medium=email

Tweet @NINDSnews, discuss this study protocol. More voices, the better.

 

[viggster]

I have not read much of this thread, but here's what I posted on another thread:

Hi Simon - I'm not privy to all of the details, but here's what I've gleaned. Vicky Whittemore seems to 'get it' - she understands the difference between chronic fatigue the symptom and ME/CFS the illness. But her boss, NINDS director Koroshetz, apparently does not get it. Now, I'm getting this second-hand so I can't 100% vouch for it. Various advocates have over the past few months had meetings with those two and have pushed for, a) a formalized role for patients and advocates in NIH research planning, and b) CCC criteria for the NIH clinical study. Neither suggestion has been acted on by the NIH team. Yesterday I sent a note to Dr. Collins explaining that things are not going well and NIH has a lot of work to do to get the patient community on board with what they're doing.

That said, yesterday Julie Rehmeyer heard from an NIH press officer that the clinical study protocol was mistakenly posted early. I hope this means there is still room for the NIH team to do a better job of listening to us. If they end up sticking with the protocol that was posted (it was not "announced" by NIH as some suggested...no one at NIH alerted anyone to it), I don't think it will be the total disaster some fear. If they do the 2-day exercise test properly, the study will find two groups of people - a group with PEM and a group without PEM. We already know these two groups exist, so the NIH is kind of reinventing the wheel here. It wouldn't be the first time an NIH intramural study unnecessarily replicated work done by outside researchers. They have a habit of doing that.

Several people are talking with the NIH team this week and expressing some of these sentiments. I hope they listen.

Brian

PS - On the positive side, the PI of the study is an expert in infections of the CNS. His name is Avindra Nath and he's known for discovering many of HIV's neurological impacts.
https://neuroscience.nih.gov/ninds/Faculty/Profile/avindra-nath.aspx

 

[duncan]

On the negative side, who ever drafted this proposed study would appear not to have a good understanding of what CFS is (or is indifferent ). So how did that happen in the first case with such a sensitive and contentious disease? Where is the due diligence and care?

Now is the time for the right message to be conveyed, i.e., that the old way of equating ME/CFS with tiredness will not be tolerated.

 

[viggster]

But worse in my view, is making the test mandatory for inclusion in the study. I would refuse point blank to do even one maximal test, as my relapses are triggered at way lower activity, and I'm sure I'm not alone. Patients willing to sign up to a 2-day test are likely to be unrepresentative of patients generally, and that's a huge issue - on top of the safety/ethical one.

That's an interesting point, but how else can PEM be documented? Sure, the study could ask participants if they experience PEM, but is there any other test that shows - with data - what PEM looks like?

I did a 2-day exercise test for my case with Prudential. It wiped me out for a good long while. So I certainly understand the fears. I don't know if I would do the test again for a study. But I don't know how else PEM can be measured.

 

[viggster]

Solve ME/CFS Initiative responded to the study protocol pretty forcefully:

http://solvecfs.org/NIH Begins Recruitment of ME/CFS Study Participants

Also, it's unclear if patient recruitment has begun, especially if the protocol has been posted prematurely.

 

[Kati]

That's an interesting point, but how else can PEM be documented? Sure, the study could ask participants if they experience PEM, but is there any other test that shows - with data - what PEM looks like?

I did a 2-day exercise test for my case with Prudential. It wiped me out for a good long while. So I certainly understand the fears. I don't know if I would do the test again for a study. But I don't know how else PEM can be measured.

i did 2 exercise tests of 2 days each for research, in the space of 10 months. (I hope it was worth it) I fare much worse now, due to that. With today's technology, is there a way to avoid post exertional relapse? Could they not study the more severely affected and pick up 'disease signals' without doing any harm?

 

[Sasha]

That's an interesting point, but how else can PEM be documented? Sure, the study could ask participants if they experience PEM, but is there any other test that shows - with data - what PEM looks like?

I did a 2-day exercise test for my case with Prudential. It wiped me out for a good long while. So I certainly understand the fears. I don't know if I would do the test again for a study. But I don't know how else PEM can be measured.

Didn't the Lights do a single submaximal test and found something looking PEM-like in gene expression in blood samples taken at intervals after the test?

I also wouldn't take a 2-day CPET. But for diagnosis purposes, is objective evidence of PEM necessary? Would it be sufficient to ask patients if they have delayed exacerbation of symptoms?

AFAIK there's no objective test for lots of conditions, just self-report - but if patients report specific symptoms, that's good enough for diagnosis (fibro, for example, and other pain & neuro conditions).

 

[viggster]

But for diagnosis purposes, is objective evidence of PEM necessary? Would it be sufficient to ask patients if they have delayed exacerbation of symptoms?

The NIH study is not about diagnosing patients - it's about gathering a huge slew of data to sort through to look for promising leads for biomarkers and treatment targets.

 

[Kati]

Didn't the Lights do a single submaximal test and found something looking PEM-like in gene expression in blood samples taken at intervals after the test?

I also wouldn't take a 2-day CPET. But for diagnosis purposes, is objective evidence of PEM necessary? Would it be sufficient to ask patients if they have delayed exacerbation of symptoms?

AFAIK there's no objective test for lots of conditions, just self-report - but if patients report specific symptoms, that's good enough for diagnosis (fibro, for example, and other pain & neuro conditions).

Don't think for an instant that fibro and chronic pain have a good reputation in the community. Diseases that have a biomarker (MS, rheumatoid arthritis for instance) get much more respect and access to research funding than diseases who rely on self-report or lack biomarkers.

Fibromyalgia is getting some of the same vilification including mentions of 'catastrophizing' and 'patients with fibro should not get access to disability insurance'. Scary.

 

[Scarecrow]

Specifically it was asymptomatic for fatigue symptoms. "had Lyme disease, were treated, and don t have fatigue symptoms"

True............but then, they seem to have managed to reduce PI-CFS to just fatigue (as they lie to keep bolding throughout the description), so I wouldn't read to much into that.

So does this mean those post-treatment arthritic knee lyme patients are acceptable as long as they don't have fatigue?

Wouldn't the arthritis symptoms potentially come under post-Lyme disease syndrome or would they be more likely to be considered general arthritis. Is there anything specific about Lyme arthritis?