Large-Scale Federally Funded Programmes

1 RECOVER-TLC Clinical Trials Programme

  • Principal Investigator:: Multiple PIs across sites

  • Institution:: NIH-funded, multi-site across the United States

  • Contact/URL:: https://recovercovid.org/

  • Registry ID:: Multiple NCT numbers (programme-level)

  • Funder:: NIH (National Institutes of Health)

  • Status:: Active; multiple trials at different stages

  • Phase:: Multiple interventional trials (Phase II–III)

  • Cohort:: Long Covid patients (with substantial ME/CFS overlap)

  • Mechanism/Focus:: The RECOVER-Treating Long COVID (TLC) programme includes multiple treatment trials:

    - *REVERSE-LC*: Baricitinib (JAK inhibitor) for
  neurocognitive and cardiopulmonary symptoms; recruiting

- *RECOVER Energize*: Structured pacing for PEM
  ($n=600$); completing December 2025

- *LDN trial*: Low-dose naltrexone for fatigue in
  ages 6–25; enrolment estimated summer 2026

- *GLP-1 agonist trial*: Targeting immune
  dysregulation; enrolment estimated late summer 2026

  • Primary Outcomes:: Vary by trial; include symptom severity, exercise tolerance, immune markers, quality of life

  • Estimated Completion:: Results from first-round trials expected by end of 2026

  • Timeline:: RECOVER programme initiated 2021; TLC trials began 2024–2025; second-round trials planning 2026

  • Publication Medium:: High-impact journals; all results expected to be open access (NIH-funded)

  • Document Relevance:: Ch. 7 (immune dysfunction), Ch. 10 (cardiovascular), Ch. 17 (pacing), Ch. 14 Speculative Cross-Disease Connections (cross-disease)

RECOVER-TLC is the largest federally funded treatment trial programme relevant to ME/CFS. While focused on Long Covid, the substantial clinical overlap means positive results are directly translatable. The baricitinib (JAK inhibitor) trial is particularly noteworthy given the JAK/STAT pathway abnormalities identified in ME/CFS (Chapter 7) and the EpiSwitch epigenetic findings. The structured pacing trial (RECOVER Energize, \(n=600\)) will provide the first large-scale evidence for pacingβ€”the most widely recommended non-pharmacological intervention in ME/CFSβ€”in a rigorous clinical trial framework. The paediatric LDN trial fills a critical gap, as most ME/CFS treatment evidence excludes children and adolescents.