USA: National Institutes of Health (NIH) intramural ME/CFS study

If anything, it’s trending lower in the ME group. I’ve no idea why some think ME is an inflammatory disorder. That’s usually one of the first things that are ruled out when people are seeking a diagnosis.

 

Because it's in the name "litis".

My CRP was never elevated, but some pwME have elevated markers.

 

Maybe because inflammation is such a big part of PEM for some of us? Including high and/or rising levels of CRP during PEM and relapses.

 

I'd love to hear thoughts from @Jonathan Edwards, @Simon M, @hibiscuswahine, @Snow Leopard, @Tom Kindlon and others on the data being discussed on this thread, ie the data from the NIH Intramural study https://www.clinicaltrials.gov/ct2/show/results/NCT02669212.

Perhaps we need a new thread as these could be really important results that we all want to discuss? @Trish What do you think?

For people like me who are kind of catching up on what happened, here's my summary (please correct me if I've got bits of this wrong!)

The original primary outcomes were:

But they explain that the pandemic stopped the exercise part of the trial:

So we only have baseline measures for people with ME/CFS and controls, but the researchers think they have found differences between the groups at baseline that are significant enough to publish (paper submitted, not yet published) and render the continuation of the trial unnecessary.

@Hutan summarised the results above. I'm going to just deal with the primary outcomes here.

The first primary outcome is now this:

And the results are (in mL/kg/min):
Healthy controls mean 16.0 (standard deviation 4.3) vs ME/CFS mean 10.6 (standard deviation 3.8)

And the second primary outcome is this:

Which as I understand it is a check of whether people are putting full effort into the test. If ME/CFS patients were putting less effort into the test than controls, then a difference between groups in the first primary outcome ATVO2rel could be explained by that difference in effort. If the ME/CFS patients were putting the same effort into the test as the controls, then a difference between groups in the first primary outcome means something.

It looks like controls and ME/CFS patients were putting adequate and similar effort into the test (unit is respiratory exchange ratio):

Healthy controls mean 1.3011 (standard deviation 0.0791) vs ME/CFS mean 1.2415 (standard deviation 0.1156)

To my inexpert eye, the Mitochondrial Extracellular Flux Assay results also look interesting, with the inter-quartile ranges for controls and patients in Pmol/min looking quite different:

Healthy controls 26.2 to 58.0 vs ME/CFS: 41.0 to 84.9

A larger proportion of ME/CFS patients needed the 40 minute tilt test stopped

Health controls 37% vs ME/CFS patients 59%

To make a real difference to the field, I think the data would need to find differences that can't be explained by deconditioning. Have we got that here, in the primary outcomes viewed together?

Do some of the other outcomes explain why ME/CFS patients switch into anaerobic respiration quicker than healthy people (have I got that right)?

I'm really looking forward to reading the paper.

 

To continue the thought process here on whether any of the outcomes explain why we might switch into anaerobic respiration quicker...

They explain that:

So is this difference in number WBCs/uL in cerebrospinal fluid meaningful?
Healthy controls mean 1.0 (standard deviation 1.124) vs ME/CFS mean 1.313 (standard deviation 1.662)

 

Yeah, they say

 

(Sorry for being off-topic but I would like to echo this. I miss his insightful comments too.)

 

The main problem was this wasn't a 2 day CPET. The fact that the researchers don't seem to be demonstrating an understanding of why this is important is a major concern. In the last 10-15 we've learned a lot about how peripheral fatigue is sensed and how it causes central fatigue from pioneering research by exercise physiologists, but for some reason a majority of ME/CFS researchers seem to have ignored this.

The RER=1.1 therefore we assume maximal effort is not strictly true, in fact was not true in my the case when I did the 2 day CPET. My RER plateaued but VO2 peaked over 2 minutes later.

The differences at the gas exchange threshold/first ventilatory threshold are the key difference and a key insight into the pathology. (and other submaximal measures such as nonlinearities in effort or EMG results if someone bothers to do that research)

So I simply don't mind if patients don't actually reach their true VO2Max.

It is important not to confuse macro with micro.

VO2Max is ultimately a measure of how much oxygen the heart can deliver to the muscle, rather than a measure of how effectively the muscle cells can take up oxygen.

The the various thresholds that are discussed occur well below maximal motor unit (nerve) recruitment, and given different activation thresholds (and physiological differences between muscle fibres, such as amount of capillarisation) there is a spectrum of the balance of metabolism going on in the muscle.
Some muscle fibres will be driven such that a majority of the energy is coming from anerobic metabolism, while other muscle fibres might not be working very hard if at all!

This is why I don't like to talk about an "anerobic threshold" as it often misleads us as to what is going on at the cellular level.

 

Not really. It's probably an error in data entry, those sound like peak RERs

 

HealthRising covered this study a few weeks ago:
Four Weeks at the Clinical Center: Brian Vastag on the Soon-to-be-Published NIH ME/CFS Intramural Study
https://www.healthrising.org/blog/2023/05/30/vastag-nih-intramural_chronic-fatigue-syndrome-study/

The progress of this study reminds me of the Truck Crash GIF, showing a crash test of a truck. Several shots show the truck hurtling toward a barrier, but the animation restarts before the crash is actually shown, creating an effect of perpetual suspense.

 

Honestly between this and P.T. Prusty's Marvelous Biomarker Circus I can't decide which is the most infuriating!

 

I'll tell you right now, if this is an episode of Let's Make a Deal, the NIH is standing in front of the door with the new car behind it and Prusty is probably next to the goat.

 

I think the NIH carnival is more vexatious. They have the institutional prestige and innumerable resources necessary to muster some progress. Prusty’s pronouncements remind me of the many watershed “breakthroughs” over the decades. A lot of bluster, but not much clinical significance I’m afraid. Do we know when the biomarker will be unveiled? Has it already?

 

Maybe the NIH is taking so long because they think that due to the controversy surrounding ME/CFS they need really solid evidence before making any claims.

That's the wishful thinking on my part, which hopes that delays mean solid evidence.

 

This is thoughtful analysis. I assume they know they’re in for a pummeling from the usual quarters. Ironclad findings in an established journal are necessary, and even then, they’ll have to prepare for the impending onslaught.

I expect the most vehement, and petulant, opposition to come from the FND sector.