Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of ME/CFS or Long COVID, 2026, Barr

[Dolphin]

https://www.mdpi.com/2077-0383/15/7/2510

Testing a Personalised Dysautonomia Management Protocol in Patients with Orthostatic Intolerance and a Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Long COVID​

Julia Barr1,2,3,
Lowri Marsden1,
Theshan Dassanayake1,
Norah Almutairi1,4,
Vikki McKeever5,
Tarek Gaber6,
Rachel Tarrant2,
Belinda Godfrey2,
Sharon Witton2 and
Manoj Sivan1,2,3,*
1
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 4SA, UK
2
Leeds Community Healthcare, Leeds LS11 0DL, UK
3
Department of Rehabilitation Medicine, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK
4
Physical Therapy and Rehabilitation Department, College of Applied Medical Sciences, Majmaah University, Al Majma’ah 11952, Saudi Arabia
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J. Clin. Med.2026, 15(7), 2510;https://doi.org/10.3390/jcm15072510 (registering DOI)
This article belongs to the Special Issue POTS, ME/CFS and Long COVID: Recent Advances and Future Direction

Abstract​

Background/Objectives:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID (LC) are complex multisystem conditions with significant functional disability. Many patients experience symptoms of orthostatic intolerance, which can be captured in some cases as Orthostatic Hypotension (OH) or Postural orthostatic Tachycardia Syndrome (PoTS) on objective testing. Conservative treatments are recommended for first-line symptom management, but there is a lack of efficacy evidence. This study aims to assess the feasibility of an 8-week clinically supervised, personalised Dysautonomia Management Protocol (DMP) in a cohort of ME/CFS and LC patients with subjective and objective evidence of orthostatic intolerance (dysautonomia).

Methods:

ME/CFS and LC patients with objective dysautonomia on the 10 min active Lean Test (LT) were recruited to an 8-week DMP, with interventions introduced cumulatively every two weeks. Interventions included increasing daily fluid intake to 3 litres and salt intake to 10 g, pacing to avoid crashes and calf activation. Baseline and weekly data collection included the LT, Composite Autonomic Symptom Score questionnaire (COMPASS-31) and Yorkshire Rehabilitation Scale (YRS).

Results:

Sixteen participants completed the 8-week program, five discontinued during the program, and one was withdrawn following a severe crash. The COMPASS-31 improved by 7.7 points from week 1 to week 8 (p = 0.045), with a medium Cohen’s d effect size of 0.55. For the same period, there was a non-significant (p = 0.16) improvement in the YRS symptom severity score by 2 points. Comparing the final two weeks of the program with the first two weeks, mean heart rate during the LT decreased by 4.8 beats per minute (p = 0.032), with a medium Cohen’s d effect size of 0.44. Adherence to the interventions was highly variable, with none of the patients able to fully employ all four recommendations.

Conclusions:

The results suggest that targeted conservative interventions could influence autonomic function and symptom reduction. However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms.

 

[obeat]

Sounds like old wine new bottles!

And of course we're going to need loads more research funding to show that this study is useless every time it's repeated.

 

[InitialConditions]

I'm not letting anyone near my calf muscles.

 

[Utsikt]

Adherence to the interventions was highly variable, with none of the patients able to fully employ all four recommendations.

Conclusions:

The results suggest that targeted conservative interventions could influence autonomic function and symptom reduction. However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms.

So the «best practice» by the dysautonomia crowd was unsustainable and produced no real benefit despite the recruitment bias and unblinded nature of the interventions.

 

[Trish]

To me that pretty conclusively shows the idea of drinking more water and increasing salt intake as a treatment for POTs or postural hypotension in people with ME/CFS or Long Covid is useless.

The only statistically significant finding was an average across the group of a small decrease in the heart rate spike on standing from just above 30 bpm to just below 30 bpm. And it took doing lean tests with 183 potentially eligible people to achieve 16 completing the study.

 

[rvallee]

There is a programming joke: how do programmers copy and paste? ctrl-cccccccccccccccccccccccccc ctrl-v. Sometimes we just smash that ctrl-c because it's annoying when we don't press the key enough and end up pasting something we didn't want.

Evidence-based medicine is the opposite, they go: ctrl-c ctrl-vvvvvvvvvvvvvvvvvvvvvvvvvvvvv. They all copy one another, and paste it way more times than is needed. Which is zero, none of this is needed or wanted by anyone this is supposed to help.

This one is slightly different, sure, not just mindless rehab with mind-body nonsense, but still, there is nothing really justifying this. Your 'programs' are never going to amount to a damn thing, it's beyond obvious that medicine has no idea what to do about problems where they don't understand the pathology. This entire 'pragmatic' approach is completely worthless.

targeted conservative interventions

These people are so freaking weird. They can't possibly not see how excessively Orwellian this is.

However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms

What do you mean "might not"? You literally calculated it, you know it didn't! What even is math? Why even do studies if results don't matter one bit?!

 

[Sean]

salt intake to 10 g​

That is more than twice the generally recommended maximum level of daily sodium intake, and more like 5-10 times the optimal.

So it delivers no meaningful benefit, and seriously increases your risk for stroke and kidney disease.

Nah. I will pass on this one.

 

[Nightsong]

Perhaps worth noting that this study, which has among the co-authors a prominent member of BACME, was funded by MEA with a grant of £49,908.08 from the Ramsay Research Fund:

https://meassociation.org.uk/wp-con...onalised-Dysautonomia-Management-Protocol.pdf

 

[Trish]

Perhaps worth noting that this study, which has among the co-authors a prominent member of BACME, was funded by MEA with a grant of £49,908.08 from the Ramsay Research Fund:

https://meassociation.org.uk/wp-con...onalised-Dysautonomia-Management-Protocol.pdf

Thanks, I saw it was MEA funded and couldn't find the amount. So they wasted 50 thousand pounds on getting 16 people to drink more water and eat potentially dangerous amounts of salt and wriggle their legs, and finding it made no clinically significant difference. Sigh. Why does a crappy piece of research cost so much of pwME's donations?

 

[Andy]

Had we seen studies looking at this before? If not then having evidence showing lack of benefit is useful, albeit disappointing.

 

[Evergreen]

The authors recognise factors affecting interpretation of their findings more than most:

The observed 4.8 bpm reduction in postural heart rate change and improvement in COMPASS-31 scores, both with medium effect sizes, suggest that targeted lifestyle interventions could influence autonomic function and symptoms. However, the magnitude of change was limited, and statistical significance might not necessarily relate to a clinically significant improvement in symptoms.

As a pilot feasibility study, the primary goal was to evaluate the potential for meaningful change that could justify investigation in a fully powered trial rather than to prove the intervention’s effectiveness in this instance.

Importantly, the structured weekly review may have contributed to perceived benefit through enhanced validation and therapeutic engagement, a factor previously recognised as critical in managing chronic dysautonomia syndromes [4,6,8,9,10,11,31]. The intensive interaction from the weekly supervised meetings could itself have influenced subjective outcomes, such as the COMPASS-31 and YRS, and as such, improvements in self-reported symptoms burden may reflect contextual factors rather than physiological change.

In addition, the reported statistical significance may represent type I error, for which adjustment with Bonferroni correction would be important in a larger scale study appropriately powered to examine efficacy of the interventions.

There's some recognition of the burden of the intervention:

When recommending conservative interventions, such as those in this program, clinicians should set realistic expectations for patients and recognise that these interventions can be burdensome. It is possible that the program activities and weekly review meetings could have contributed to fatigue for participants. It is likely that, if individuals are given more time to implement changes with lower frequency of follow-up, adherence to the interventions could improve, which might allow patients to pace effectively, thereby making changes more detectable.

but no report of why 10 of 32 declined participation or 5 dropped out. I would not have been able to attend weekly appointments for 8 weeks at any severity.

I'm interested in the fallibility of testing in this area, so this caught my eye:

Among those with ME/CFS (n = 11), four had a consistent PoTS profile across assessments, with others alternating between PoTS and OH (n = 4) or PoTS and borderline readings (n = 3). In LC (n = 5), three showed alternating among PoTS, OH, and borderline profiles, with one each alternating PoTS/OH and PoTS/borderline, as detailed in Table 5. These findings highlight an individual’s variability in dysautonomia profiles and the potential for day-to-day phenotype shifts.

Serial 10 min LT testing revealed that, although most patients are consistent with one dysautonomia profile, there are patients who fluctuate between PoTS, OH, and borderline profiles, which has not previously been reported in the searched literature. Fluctuation in profiles may reflect measurement variability and inconsistencies or daily autonomic fluctuation. This variability complicates diagnosis and monitoring, suggesting that single-point testing may underestimate disease burden. Future protocols should consider timing LT assessments at the time of day when the patient is most symptomatic and incorporate repeated measures to capture these fluctuations.

 

[Turtle]

10 researchers (added to the pile) who are clueless about what they are doing,
The limitations @Evergreen summed up what they learned.
None concluding: let's stop pretending we can be usefull.

 

[Trish]

That sounds like they are gearing up to seek large funding for a much bigger trial. But what is the point when the feasiblity looks dubious, so few of those screened were eligible and measures fluctuated as much over the weeks, and the end of trial results were so weak.

 

[rvallee]

But what is the point when the feasiblity looks dubious

Academic citation stonks go up. The clickfluencer economy feeds itself on its own waste.