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Accepted for/Published in: JMIR Research Protocols

Date Submitted: Aug 19, 2025
Date Accepted: Dec 9, 2025

The final, peer-reviewed published version of this preprint can be found here:

Effectiveness and Safety of a Supplement Containing a Pharmacologically Active Basidiomycete Mushroom for Chronic Fatigue and Post–COVID-19 Fatigue Syndrome: Protocol for a Randomized Controlled Trial

Xun Y, Fong TL, Chen G, Feng Y, Chan L, Wang N

Effectiveness and Safety of a Supplement Containing a Pharmacologically Active Basidiomycete Mushroom for Chronic Fatigue and Post–COVID-19 Fatigue Syndrome: Protocol for a Randomized Controlled Trial

JMIR Res Protoc 2026;15:e82633

DOI: 10.2196/82633

PMID: 41558017

PMCID: 12869150

Effectiveness and safety of CP003 on chronic fatigue and post-COVID fatigue syndrome: A Study protocol for a randomized controlled trial

  • Yunqing Xun; 
  • Tung Leong Fong; 
  • Guang Chen; 
  • Yibin Feng; 
  • Linda Chan; 
  • Ning Wang

ABSTRACT

Background:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is characterized by persistent, unexplained exhaustion unalleviated by rest, with pathophysiology distinct from underlying medical conditions. The diagnostic complexity arises from symptom overlap with other disorders and the absence of definitive biomarkers, contributing to limited therapeutic options in current medicine. Lingzhi, a pharmacologically active basidiomycete mushroom, has been empirically utilized in Traditional Chinese Medicine (TCM) for two millennia. The study has a dual focus: (1) systematically evaluating its efficacy and safety in managing chronic fatigue and post-COVID fatigue syndromes, and (2) elucidating its clinical associations with inflammatory, immune, and oxidative stress biomarkers to uncover potential therapeutic mechanisms.

Objective:

The study has a dual focus: (1) systematically evaluating its efficacy and safety in managing chronic fatigue and post-COVID fatigue syndromes, and (2) elucidating its clinical associations with inflammatory, immune, and oxidative stress biomarkers to uncover potential therapeutic mechanisms.

Methods:

This randomized, waiting list-controlled trial will enroll 130 participants in Hong Kong, equally allocated (1:1) to either the CP003 intervention group or a waitlist control group. The intervention period spans 6 weeks, followed by a 6-week follow-up phase to assess sustained effects. The trial data will be managed using REDCap, analyzed via intention-to-treatment with IPW for missing data, assessed through generalized linear regression (adjusted for covariates and interaction terms) at 6/12 weeks, and supplemented by subgroup/sensitivity analyses in R, with results reported as mean differences (95% CI) and p<0.05 considered significant.

Results:

This study will provide experimental data on effectiveness and safety of CP003 on chronic fatigue and post-COVID fatigue syndrome.

Conclusions:

This study will provide experimental data on effectiveness and safety of CP003 on chronic fatigue and post-COVID fatigue syndrome. Clinical Trial: ClinicalTrials.gov NCT06739720. Registered on 16/12/2024.


 Citation

Please cite as:

Xun Y, Fong TL, Chen G, Feng Y, Chan L, Wang N

Effectiveness and Safety of a Supplement Containing a Pharmacologically Active Basidiomycete Mushroom for Chronic Fatigue and Post–COVID-19 Fatigue Syndrome: Protocol for a Randomized Controlled Trial

JMIR Res Protoc 2026;15:e82633

DOI: 10.2196/82633

PMID: 41558017

PMCID: 12869150

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