Dr Alan Moreau's new, low-stress protocol for provoking PEM.[Thoughts?]

[Sly Saint]

Might it be a good idea for Moreau to liaise with @Leonard Jason on this re his PEM questionnaire?
(combined with whatever objective measurements are being collected).
and presumably Moreau and Davis are 'comparing notes' with nano-needle saline stress test?

 

[MarcNotMark]

There is a case that we need a different test based on the patient’s severity. But also on how easily they get post exertional malaise, which isn’t simply a function of severity. Ideally, you would have a type of test, or a level of test, that is appropriate for each individual patient so they get stressed the right amount, and not too much.

In that case, how would you stress "healthy controls", let them run a marathon?
It may be a good test but with applying different stress levels rather difficult to compare the outcomes.

 

[NelliePledge]

In that case, how would you stress "healthy controls", let them run a marathon?
It may be a good test but with applying different stress levels rather difficult to compare the outcomes.

Maybe it would be useful to find out what level of activity a healthy would need to provoke the same level of reaction. So this could then be scientifically equated rather than patients saying they feel like they’ve run a marathon it could be shown to be the case.

 

[andypants]

Maybe it would be useful to find out what level of activity a healthy would need to provoke the same level of reaction. So this could then be scientifically equated rather than patients saying they feel like they’ve run a marathon it could be shown to be the case.

If healthy people have that kind of reaction at all, who's to say they do as long as we don't know what or why the reaction actually is?

ETA: This is one of the valuable potential results from the CPET studies with blood samples, I think. That we can look for what will cause a similar response in healthy people, or if they do at all.

 

[Dr Carrot]

Shouldn’t we also be stressing non-healthy controls who don’t have ME, to see if the response is unique to those with ME or simply a response that is found in other illnesses too?

 

[Chris]

If ever the biomechanical stimulation device had not produced sufficient physiological responses, I think prof. Moreau had a back-up plan such as using a treadmill but his early results showed that the former was more than enough to trigger measurable anomalies.

Personally I see this device really just as a means while measuring stress-activated miRNAs is the end, otherwise if testing the effectiveness of the procedure was an end in itself in this research (though not the only one obviously, that would be, er… solving ME…) the presence of the nurse for 90 minutes would muddle all results. As others have said interacting with that nurse and all the brain activity this requires (an active brain consumes up to 30% of the oxygen our entire body uses…) surely triggers an amount of miRNA expression alongside the massage and it would be impossible to know what comes from the device and what comes from the interaction.

As for the question whether the massage is still too light a stimulation to measure full blown PEM, maybe we can think that this procedure allows to measure the very initial processes that could lead to PEM. PEM is about crossing thresholds (except for those related to other factors than exertional ones such as food intolerances) but it could be that even the most carefully paced activity is already activating discrete factors that could lead to PEM; and it may also be that, with people who have PEM 24-48 hours after having crossed their threshold, in those cases the process had begun nonetheless the first minute the threshold was crossed, but simply was not felt in any way by the patient. It would make little sense (to me…) that in delayed PEM there would be zero physiological response whatsoever following exertion, and then the effects suddenly begin 2 days later ex nihilo so to speak (much like getting a cold: the second the virus is in your body things start happening, but you only feel the first signs 1-2 days later). Under this angle this test could be seen as trying to pick up a PEM's starting point as far as miRNAs go, that might eventually lead to domino effects and mayhem all over the body, even if the test does not trigger the full PEM storm.

 

[andypants]

Thanks, @Chris that was very enlightening

 

[Trish]

it would be impossible to know what comes from the device and what comes from the interaction.

Could be done by testing the same person on separate occasions with just the conversation, the conversation plus the massage and just the massage.

I think you make a good point about PEM being the tipping point in a process that begins when activity begins and is only reached if activity is too much for that person on that day.

The biological processes can be measured at any stage. But if you don't actually do enough to send the person into PEM, you might miss some other miRNA change that only happens if PEM is triggered.

 

[Dechi]

Just wanted to say thank you for doing both of these tests, I think that is amazing.

I also wanted to ask if the sleep problems were wired yet tired/exhausted/fatigued or were more of more sleep needed. I think the two differences are part of the problem as in two different parts.

Second thing is do you think that the CEP test is too much to expect to put patients through.

Always glad to help with any ME study I can get into ! -)

The sleep problems were probably a mix of tired but wired and insomnia, my usual sleeping problems. Sleepiness happens to me sometimes, but it’s not frequent.

The 2-day CPET test is definitely very, very hard for us, and I would even dare say harmful, even though it can be of great help for disability purposes. If I didn’t have to, I would not have done it. I am considering doing it again, this time for the research purposes, but only if my baseline improves.

 

[Tilly]

Always glad to help with any ME study I can get into ! -)

The sleep problems were probably a mix of tired but wired and insomnia, my usual sleeping problems. Sleepiness happens to me sometimes, but it’s not frequent.

The 2-day CPET test is definitely very, very hard for us, and I would even dare say harmful, even though it can be of great help for disability purposes. If I didn’t have to, I would not have done it. I am considering doing it again, this time for the research purposes, but only if my baseline improves.

With regard to wired but tired, I think they should track this more closely and for longer. I think the PEM goes in a circle/cycle and can indicate when recovery is starting.

So Baseline > activity > surge of lactic acid > wired tired > more symptoms > if you rest you then get less symptoms > less wired and tired > more ability. If you at this stage do any more activity before you go back to baseline then the PEM sets in quicker and deeper and takes longer to recover.

I wonder what the bloods would show at the end of recovery, say 6 months after?

As for doing another CEP test, that fills me with cold chills and makes you an endurance athlete and an #MEhero

 

[Tilly]

Maybe it would be useful to find out what level of activity a healthy would need to provoke the same level of reaction. So this could then be scientifically equated rather than patients saying they feel like they’ve run a marathon it could be shown to be the case.

There are enough Marathons being run to take a questionnaire to?

 

[Tilly]

Could be done by testing the same person on separate occasions with just the conversation, the conversation plus the massage and just the massage.

I think you make a good point about PEM being the tipping point in a process that begins when activity begins and is only reached if activity is too much for that person on that day.

The biological processes can be measured at any stage. But if you don't actually do enough to send the person into PEM, you might miss some other miRNA change that only happens if PEM is triggered.

They should also track the recovery. Not so much the time it takes but what happens to the body as it tries to even they systems out. By tracking this they will get an individual response. Track that with others and you will get the bigger picture?

Problem funding?

 

[Mithriel]

I think that naming it a protocol for provoking PEM is misleading. As others have said it is more about looking at the starting process that eventually becomes PEM. That would be a great thing to test for as it would be much less likely that patients would suffer because of the test itself. It's all mixed up because we are also trying to prove we get PEM, not just deconditioning ...

Many years ago, possibly before the invention of CFS, a doctor who treated ME patients said that when a patient came to their first appointment the nurse gave them paper and a clip board and asked them to write down a history of their illness. With ME, the handwriting started off well but got worse and worse. There are so many small muscles and nerve fibres used for the complex process of writing that it has always seemed to me to be an ideal place to find problems with stamina or whatever the word is for what many of us experience - a sudden drop in ability that is totally unlike that experienced by healthy people or pre illness.

 

[Simon M]

Thanks for all the replies.

The main comment seems to me that, while the protocol clearly has an effect on (most0 patients, as well as biological effects, there are doubts as to whether this amounts to full post-exertions malaise. That view is reinforced by the two people to have undergone the protocol who kindly share their experiences:

I would say this does not really provoke full PEM, just the immediate response to exertion that have been found in other studies.

I remember I had fatigue from the test, maybe more difficulty sleeping. But nothing even remotely as bad as the 2-day CPET test (I crashed for 3 weeks).

In case it wasn’t clear, Alain Moreau presented this as a new end effective protocol, but the suggestion that it had potential to be used much more widely in the field was mine. Given the feedback here, I don’t think I will be pursuing this idea.

 

[NelliePledge]

They should also track the recovery. Not so much the time it takes but what happens to the body as it tries to even they systems out. By tracking this they will get an individual response. Track that with others and you will get the bigger picture?

Problem funding?

What do you mean by recovery here recovery from an exertion or recovery from the illness?

 

[rvallee]

They should also track the recovery. Not so much the time it takes but what happens to the body as it tries to even they systems out. By tracking this they will get an individual response. Track that with others and you will get the bigger picture?

Problem funding?

They're not funded by government. It's a private grant from a foundation so likely pretty small. I think the strategy is to build up to hypothesis-testing so CIHR (the NIH-MRC equivalent for Canada) will release some of the $1.8M they have so far kept untouched.

 

[rvallee]

Thanks for all the replies.

The main comment seems to me that, while the protocol clearly has an effect on (most0 patients, as well as biological effects, there are doubts as to whether this amounts to full post-exertions malaise. That view is reinforced by the two people to have undergone the protocol who kindly share their experiences:



In case it wasn’t clear, Alain Moreau presented this as a new end effective protocol, but the suggestion that it had potential to be used much more widely in the field was mine. Given the feedback here, I don’t think I will be pursuing this idea.

I think that's the idea, to have a test that can be deployed much more widely. It's portable and way cheaper than CPET but also doesn't provoke serious deterioration, which is a hard sell for CPET when the hypothesis is "this could cause severe long-term harm to the patient". Which is of course massively ironic when the harm isn't recognized by itself...

The hypothesis seems to be this provokes a light reaction, the early stages perhaps, of PEM. I'm seeing it like an allergy blot test compared to "here's some peanuts, I hope you don't go into anaphylaxis".

 

[Tilly]

What do you mean by recovery here recovery from an exertion or recovery from the illness?

Sorry that is confusing (I use that term for my son, it makes it easier on him emotionally) recovery back to base line. I need a better way of explaining.

 

[Tilly]

They're not funded by government. It's a private grant from a foundation so likely pretty small. I think the strategy is to build up to hypothesis-testing so CIHR (the NIH-MRC equivalent for Canada) will release some of the $1.8M they have so far kept untouched.

True and the fact they kept funds untouched or in some cases used for other research is enough to my egg boil.

 

[Ravn]

In case it wasn’t clear, Alain Moreau presented this as a new end effective protocol, but the suggestion that it had potential to be used much more widely in the field was mine. Given the feedback here, I don’t think I will be pursuing this idea.

While it may not be ideal I think the cuff test is worth pursuing, for two reasons.
1) It's something that can be used on patients too severe to ever get near a CPET.
2) It measures something: resulting miRNA patterns differed between ME patients and controls and, if I recall correctly, also between ME and fibro patients. And even if that something isn't full-blown PEM it still seems to be ME-specific (this would need to be tested against more diseases), so well worth exploring.