Open (Melbourne, Australia): Baker Institute - Understanding exertional and orthostatic intolerance

https://www.emerge.org.au/get-involved-in-research/

Have you been diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or orthostatic intolerance?
Researchers at the Baker Heart and Diabetes Institute (Melbourne, Victoria) request your contribution to research that hopes to understand post-exertional and orthostatic intolerance

Patients interested in participating in this study need to satisfy the below requirements:

• Diagnosed with ME/CFS and/or orthostatic intolerance (Postural Orthostatic Tachycardia Syndrome- POTS, or orthostatic hypotension)
• Healthy controls/volunteers also welcomed to particpate
• Are aged 18 years or older

If chosen for this study, participants will need to attend two clinic visits at the Baker Heart and Diabetes Institute. During these visits, participants will complete a cardiopulmonary exercise test (CPET) and provide a small blood sample before and after the exercise. Each visit will last approximately 2-3 hours (Parking and time spent reimbursed).

Following the clinic visits, participants will be asked to complete online questionnaires and wear a device to monitor blood pressure for 5 days at home. Additionally, there is an optional MRI (brain scan).

For more information or to register your interest, please feel free to contact the researchers at the Baker Institute conducting the study:

Email: Elena.Christopoulos@baker.edu.au

 

I'm guessing it's related to this research funding announcement from earlier in the year:
https://www.s4me.info/threads/baker...cts-of-long-covid-plus-pots-and-me-cfs.38947/

 

It seems a pity that the advertisement tells people nothing about what it is investigating. Should researchers assume that patients are so dumb or uninterested in what is the idea is that they don't want some real information?

I have a nasty suspicion that it is not thought to matter. The point is just to prove that exercise is good for you.

 

I contacted them earlier in the year but then backed out of actually doing it as I was in a downward spiral at the time and worried about gettin worse. Here's the email they sent me. I think the research objective looks good and I should follow up with them!

Hi ,


Thank you for completing the pre-screening survey and I would like to let you know that you're eligible for the study.


For this study we’re trying to understand the autonomic nervous system’s (ANS) recovery in regard to post-exertional malaise in people who have ME/CFS a little bit more as there seems to a be stunted recovery of the ANS and compare them to healthy controls. So, we get participants to fill out some questionnaires, complete a cognition assessment, a blood draw (if consented to it), a resting ECG, a spirometry test and a CPET. After the CPET, we then take a few more bloods and fill out a questionnaire. After the visit, we then send some of the questionnaires again and the cognition assessment to be repeated at a few different timepoints (24-hrs post visit; 48-hrs post visit; 72-hrs post visit; and 7-days post visit). I have also attached the PICF for you to have a read through.


If you're happy to go ahead, please let me know so that we can schedule an appointment for your visit at The Baker. The visits usually last for at most two and half hours and we run them in the mornings of Wednesdays and Thursdays. The next available dates are May 22nd, June 5th and June 6th.


Please don't hesitate to contact me if there are any questions/concerns Have a lovely day!

 

Maybe not, I got it from checking the investigators publications on PubMed. They are almost all about the value of exercise - with a focus on the value of exercise in fatigue in people who have had chemotherapy for cancer.

 

Presumably they mean exertional intolerance rather than post-exertional intolerance. The presumed running words together with PEM isn't very encouraging.

I would hazard a guess that the interest is in discovering why exercise is good for some people and not others, when in reality it probably isn't that good for anything much in itself.

 

I missed the message from Murph earlier.
I think those comments are fair @Hutan.

I have no idea even what 'ANS recovery' would be, to be honest. The ANS is constantly responding to all sorts of things. If it is in a bad way, I doubt it 'recovers' after exercise, it just keeps doing the wrong thing - and the same another time.

It would be good if all researchers asked S4ME what they think before finalising a project or a paper (some are doing that, yes). That would be patient involvement come of age.

 

It seems that 'ANS recovery' is a technical term used in high performance athlete physiology for return of heart rate variability to baseline after strenuous exertion (maximum or near).

I am not sure why heart rate variability should be telling us anything interesting in relation to PEM or indeed why it should be considered a sign of 'ANS recovery'. Maybe it should be 'termination of the exercise-related ANS response'.

The paper that first pops up on Google for ANS recovery talks of HRV returning to baseline between 10 and 90 minutes after exercise, with highly trained athletes showing quicker return than just trained (?did I nearly hear 'deconditioned').

I worry that the hypothesis is that people with ME/CFS just need to train more to shorten their 'ANS recovery' and get rid of their PEM.

Of course ME/CFS could be due to dysregulation of acetyl choline signalling, including in the parasympathetic system. And this might be a clever way to get a clue to that. It would just be nice to know a bit more about the thinking involved.

 

Just from athlete speak perspective she’s got this wrong. I talk of jog back recoveries to ‘get fitter’ where you are ‘recovering to do again’ and then there would be ‘proper recovery to perform’ which would be that no athlete would be doing a heavy training session the night before a big race. That’s obvious for anyone who watches eg athletics and heard commentators talk about the rounds in competitions like the olympics and how having a semi close to a final affects the likelihood even a champion can do a pb to break that record.

I guess for athletes that’s ’recovery recovery’ where whatever that number of days is they’d have ideally before competition or after competition before they do a heavy session. I believe they actually get a few weeks of proper rest at some point after a season.

and it’s not the 10 or 90 minutes.

the reason jog back recovery is used is only to get fitter by somehow forcing the body to go again before fully recovered. Catch your breath and go again. I guess maybe that’s about heart rate , not sure though, probably lots of other things that are nothing to do with autonomics - including anaerobic stuff.

Given this is what I was doing up to and overlapping with developing ME I’m pretty sure, then I’m highly doubtful this is the solution.

I do think the issue and the clue of PEM if someone is actually able to properly get the basics of that makes it obvious the issue is with the recovery-recovery if not all then to a big extent. I remember being a newbie doing those sessions of jog backs vs years on and it’s very different to having ME.

hence why it was 2DAY cpet.

It’s interesting that we aren’t all ‘unfit’ vs other controls (depending where we started, how ill, length of time) in judgy non-medical terms. But I agree with @Keela Too ’s point in another thread the main thing is we can’t ’get Fitter’ but the opposite happens if we put ourselves through these processes. I think at least many weeks down the line, for many it will become obvious over months but be really obvious in serious lower function in normal person terms they’d be horrified with but what’s horrifying is their not listening or hearing it. I suspect it shows in performance a lot earlier if you are an athlete but not in clinics because of the coercion causing everything else to be stripped from their lives before the GET in compensation.

It sounds like just as some hear exercise as the only issue so you use exertion to emphasise it’s all sorts including thinking or talking vs threshold perhaps if you are functionedly fixed by a certain areas language you hear exertion and think ‘effort’ or heart rate zooming up like a fear response is an issue.

We get research sponsored based on thesaurus instead of anyone wanting to hear the nuance of what’s going on.

so I’d indeed have been interested for these things to be talked about in expanded unambiguous terms not hidden behind these things.

 

Here's the PICF. It contains some language that will make some people concerned. And some stuff that looks good.

The language some people might be concerned about: " It will also help inform people with ME/CFS what levels of activity might decrease the risk of PEM and guide doctors in designing rehabilitation programs."

The stuff that looks good: " The research project examines how the autonomic nervous system (ANS) responds to exercise. and whether that response causes post-exertional malaise in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Post-exertional malaise (PEM) is the worsening of ME/CFS symptoms after mild physical or cognitive activity."

• The most optimistic take is that if they find a genuine link from autonomic dysfunction to PEM we could get a way of figuring out our pem thresholds ex-ante rather than our current approach of discovering we've breached them ex-post.
• A middle ground might be they see that exercise usually causes PEM and the data is muddy.
  
• The least optimistic take is that this is a figleaf for a plot to keep GET alive and no matter what the results are it will be shoe-horned into a recommendation for more exercise.

I've long wanted scientists to study the cardinal symptom of this disease, PEM. And I am afflicted by a severe lifelong case of optimism, i'm sorry to say, so I'm excited to see what the study finds!

 

How can they answer the bit:

‘and whether that [ANS] responses causes PEM’?

 

The Baker Institute copped a lot of criticism after the announcement of a trial of GET for Long Covid:

Long COVID study tests using exercise to overcome symptoms

(S4ME thread here)

I get the impression that Emerge has tried to educate them about PEM since then.

Whether this study is a genuine effort to investigate PEM or whether it's to demonstrate to us deluded people with ME that exercise will improve us, I can't tell.

 

I still cannot get a clear idea what the study is trying to discover.
If they are interested in 'ANS recovery' presumably they would need to monitor heart rate for at least two hours after the exercise? We are not told what the blood tests are measuring at all. Maybe they include adrenaline or acetylcholine but I am not sure how useful those would be.

As has been asked, it is not clear how they would establish that shifts in ANS recovery caused PEM.

One thing this and other CPET studies raises for me is the appropriateness of a CPET test as a way of studying triggering PEM. Anyone who realises that a CPET test would trigger PEM for them is likely not to volunteer. And is a CPET test a realistic example of the problem? My guess is that if I had ME/CFS and had to take part in such a study, the hassle of getting to the lab and hanging around, changing, having blood taken, finding somewhere to park, getting home in traffic, might far outweigh the impact of a few minutes on a bike (already assuming I was well enough to undertake that).

I am sceptical about all the stuff about anaerobic thresholds being relevant to PEM, especially if it can occur after mental effort or a long train journey. The CPET test has been used in ME/CFS because it provides precisely measurable physiological indices like VO2max, that have been suggested can be used to show a shift in physiology on a second test that might be indirectly relevant to PEM. But measures on a single test are not very informative. Moreover, riding a bicycle as hard as possible for 20 minutes isn't a particularly sensible way to try to trigger PEM as far as I can see. It is no way typical of what triggers PEM in real life.

The bottom line for me is that if scientists are asking patients to undergo procedures that by definition are supposed to be making them more unwell, they ought to explain in terms that at least a seasoned scientist can understand what they are trying to discover and whether it has any real chance of being useful. I don't get that here yet.

 

Hoorah! Precisely, thank you for saying that.


And of course as we all know you can stitch up these tests by making people do a few of these and benefit from claiming the effect that is only caused by x 'which was a controlled dose' when actually it will always be caused by people having found a better journey to the test itself over the space of doing more of the tests and finding the right car park, drop-off, asking to lie down in the waiting room, knowing where they are going and booking the day off work before etc

On this one are people going home afterwards or lying down in a room there that will be controlled for noise etc? Because I'm not in rest until I'm somewhere really suitable. And getting home faster because you'd nailed the journey home (and asked to change the time to avoid rush hour) is what will be affecting that HR coming down.

And by now they all know or should know that pwme will have to do that. And the more unmanageable the task the more filtered the applicants and more adjusted those unaccounted for 'extras' to the task end up being. Because if they don't then they end up as a drop-out not counted in results anyway because the exhaustion is cumulative. And human beings have to learn to cope with what they've signed up for.

I think that 'inadvertent con' needs to be worked on very hard by any allies and patient community. Claiming it is a 'controlled dose' by putting your fingers in the ears to what the condition involves and basic scientific method where you need to control for actual underlying confounding causes.

What she is potentially mainly measuring is 'was doing my session less stressful as it went on' (with underlying causal factors like a noisy room getting less noisy, getting home to bed quicker, slickened up journeys and doing less other commitments around later tests etc) not what she claims she is. OR worse: Krypton factor filter of 'those who got to the end were the most well'.

I'm bored of that exact same 'loaded' experiment being re-run in so many different forms, with no proper null and dodgy claims from correlations - it is time that no committee is allowed to sign off anything for ME/CFS without filling out forms confirming they have absolutely designed this out and will be accounting for anything left in their limitations. Properly. Because it makes research a charade otherwise.

In psychology you would actually do experiments where you 'hide the lead' so not to influence results, like tell people they are playing a game to see reaction times when it's about mood when they turn up the central heating on it. Until we sort this issue all of these are potentially just that but the same actual experiment/phenomena being re-run: the Krypton Factor Filter + making the total load around the task more manageable.

So I don't understand why things like how 'disorganised' the admin is, ie how much hanging around and walking to find places etc for the starter measure (vs later ones) don't have to be detailed in task sheets, monitored independently as I almost imagine the potential for when eg kids on their first day of school are encouraged not to do too well on their reading test because it's their progress that is being assessed at the end of the year vs that.


- this time to try and rename raised heart rate means 'ANS' instead of 'body being put under stress'. She could run just heart rate if she wants, and call a spade a spade without putting inference on it - if that is what she is measuring call it exactly that.

If she thinks she is 'looking into PEM' then she's overshot her start-line by about 5miles because she doesn't understand what it is. Noone does, so how is she measuring it? When/over what time-period? Which objective tests? and what do they precisely tell her?


And does she get this misses that same point that all the rehabbers do which is that getting people to 'be able to do more' for a few months isn't the hard bit. We just can't do it without deterioration 6months after that. Which is the actual illness part. SO where is the measure that any of this leads to help and not harm, by checking at 6, 12, 18, 24, 36months?

 

That's an interesting idea. But if they're trying to understand how PEM might be generated, wouldn't the study also need to take samples whilst it's developing and once it's underway?

It's not easy, as there's a good chance some of the shifts take place during sleep. People who're well enough to trigger PEM by doing physical activity often report waking up with it—they might have all the symptoms or only the early signs of it, but something has changed from the previous night. It seems unlikely it could be unravelled from Holter monitor data, which seems to be all the researchers are doing post-stimulus.

 

Maybe, or maybe you could pick up an inappropriate acetyl choline signal early on after exercise that correlated with later PEM. But I am not even clear that you can measure ACh in blood or what the bloods they are doing are.

I guess the Holter monitor is to look at heart rate variability returning to normal and trying to correlate a delay in that with PEM later. Trouble is that there is bound to be some correlation but not complete correlation. I am not sure where that gets you.

 

I always find the adrenaline surge doesn't come in until near the point of exhaustion on Day 1. It's the reason I often don't sleep that night, and often find it impossible to resist doing yet more activity on Day 2.

Day 3: face down.

So for me, the surge could just as well be one of the drivers of PEM.