Protocol Pursuing Reduction in Fatigue After COVID-19 via Exercise and Rehabilitation PREFACER: a protocol for a randomised feasibility trial, 2025, Billias+

[SNT Gatchaman]

Pursuing Reduction in Fatigue After COVID-19 via Exercise and Rehabilitation PREFACER: a protocol for a randomised feasibility trial

Spoiler: Authors

Nicole Billias; Dimitra V Pouliopoulou; Arden Lawson; Victoria D’Alessandro; Dianne M Bryant; Sue Peters; Alison B Rushton; Erin Miller; Laura Brunton; Shannon McGuire; Michael Nicholson; Trevor B Birmingham; Joy C MacDermid; Kieran L Quinn; Fahad Razak; Susie Goulding; Panagis Galiatsatos; Emily Saunders; Jacquelyn Marsh; Tiago V Pereira; Pavlos Bobos

INTRODUCTION
Over 777 million COVID-19 infections have occurred globally, with data suggesting that 10%–20% of those infected develop Long COVID. Fatigue is one of the most common and disabling symptoms of Long COVID. We aim to assess the feasibility and safety of a new, remotely delivered, multimodal rehabilitation intervention, paced to prevent post-exertional malaise (PEM), to support the conduct of a future, definitive randomised trial.

METHODS AND ANALYSIS
We will conduct a randomised, two-arm feasibility trial (COVIDEx intervention vs usual care). Sixty participants with Long COVID will be recruited and randomised prior to giving informed consent under a modified Zelen design using 1:1 allocation with random permuted blocks via central randomisation to receive either the COVIDEx intervention or usual care. The 50-minute, remotely delivered, COVIDEx intervention will occur twice weekly for 8 weeks. All participants will wear a non-invasive device throughout their entire study participation, to track heart rate, blood oxygen saturation, steps, sleep and monitor PEM. The primary feasibility objectives will be recruitment rates, intervention fidelity, adherence, acceptability (intervention and design), retention, blinding success and outcome completeness. Secondary objectives will include refined estimates for the standard deviation and correlation between baseline and follow-up measurements of fatigue. Feasibility and clinical outcomes will be collected at baseline, 4, 8, 12 and 24 weeks. Qualitative interviews with participants and physiotherapists will explore intervention acceptability and barriers/facilitators.

ETHICS AND DISSEMINATION
Ethical approval for this study was obtained by the Western University Health Sciences Research Ethics Board (REB# 123902). Dissemination plans include sharing of trial findings at conferences and through open access publications and patient/community channels.

TRIAL REGISTRATION NUMBER
NCT06156176

Web | PDF | BMJ Open | Open Access

 

[SNT Gatchaman]

A subgroup of patients with Long COVID may indicate that they experience PEM on the pre-screening and demographic questionnaires. PEM is defined as new or worsening symptoms (such as difficulty thinking, problems sleeping, sore throat, headaches, feeling dizzy or severe tiredness) up to 48 hours after a physical or mental activity that would not have caused a problem before COVID-19 infection and subsequent post-COVID-19 fatigue. Symptoms of PEM can last for days, weeks or months. We will address PEM in the trial by the following:

a. Pacing the COVIDEx session to reduce over-exertion. A pacing strategy and protocol may reduce exacerbation of PEM for those with Long COVID. Pacing will entail frequently gathering subjective measurements of intensity from participants, as well as ensuring that all components of the session (ie., cardiovascular, strength training) have adequate rest and recovery in between periods of more intense activity. Participants will inform the physiotherapist or exercise instructor of their resting heart rate and blood oxygen levels before each session and after each component of the session, which will help determine the rehabilitation intensity and pacing.

b. Monitoring correlated measures for blood lactate levels in participants. People with Long COVID may experience skeletal muscle abnormalities, such as mitochondrial and endothelial dysfunction, and a change to primarily anaerobic metabolism and glycolytic muscle fibres. These changes can reduce movement capacity and potentially trigger PEM. Potential causes for these skeletal muscle abnormalities include deconditioning, local tissue hypoxia, autoimmunity, electrophysiological changes and central fatigue (neurological alterations). Monitoring correlated measures for blood lactate enables examination of these metabolic responses (ie, mitochondrial dysfunction, reduced tissue oxygenation) in people with Long COVID, which could help prevent the onset of PEM by ensuring participants do not exceed a threshold that could induce PEM.

Specifically, our objective of monitoring correlated measures for blood lactate is for safety purposes to prevent overreaching in participants with Long COVID. All COVIDEx participants, throughout the COVIDEx sessions, will use a smart watch to monitor correlated measures for their blood lactate levels, specifically heart rate and blood oxygen. Steps activity and sleep will also be monitored to track physical activity and sleep disturbances. […] If oxygen saturation falls below 92%, participants will be advised not to take part in (or discontinue) the session, and this will be recorded promptly.

 

[Utsikt]

I struggle to see how this will add any value.

All of the proposed outcome measures are subjective, except for the sit stand test and step count.

The rationale behind certain blood lactate thresholds (through proxies) being «safe» is not sound.

There is no run-in prior to the intervention to get a long term baseline for the participants.

The participants will know if they are in a group where it’s expected to observe improvements, so the blinding measures won’t improve the risk of bias for the subjective outcomes, even though they have eliminated the nocebo argument for the CAU group.

 

[MaudSac]

PaEM do not need clinical trials on pseudo "PEM cautious"/paced physical rehabilitation (doomed to failure) ; we need clinical trials on treatments to cure the disease, or at least alleviate the most debilitating symptoms.

I my opinion, this is yet another waste of money.

 

[rvallee]

The bullshit wheel needs to be constantly spun or it stops spinning. It has been determined that the wheel must keep spinning, as otherwise things would be embarrassing, and so the value of this research is to simply keep spinning the wheel.

Every old program is old and new again. Always new. There are always more new programs in the banana stand.

 

[rvallee]

The primary feasibility objectives will be recruitment rates, intervention fidelity, adherence, acceptability (intervention and design), retention, blinding success and outcome completeness.

This is a trial of the idea of conducting a trial. Not a single one of those have anything to do with anything patients need. It's all about checking boxes.

Can a trial of exercise be performed? Can the proper boxes be checked? Gee, I don't know. Judging from the LITERALLY HUNDREDS, it's kind of hard to tell. But I'm sure one more will not do anything but spin the wheel of bullshit, which is needed for the wheel's ability to keep on spinning. Perpetual motion, if one ignores the motion needed to keep it perpetually spnning.

Spiiiiin the wheeeeeeeel.

Looking back from hundreds of such trials performed over several decades: what has actually been learned? What is a single thing that anyone involved in this can assert they didn't know before? Not a single thing has been learned. Literally not a single bit of information. None of this has anything to do with research, with what patients need or has any chance of alleviating anyone's suffering.

Spiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiin the wheeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeel!