Summary
Melatonin is tracked by OSMF as an investigational option for Long COVID; no regulator has approved it for this indication, and most post-viral conditions have no approved disease-modifying therapy at all. ClinicalTrials.gov lists 2 registered trials linking Melatonin to Long COVID: 2 have completed. The most advanced is Phase 2 (NCT06404086, sponsored by Duke University). It plans or enrolled 830 participants. Registered activity dates to 2024. The literature layer holds 13 publications for this pair: 1 systematic review, 1 clinical trial publication, 2 curated references and 9 other publications. The dated items are from 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
Long COVID / PASC is tracked on the OSMF post-viral programme alongside ME/CFS, Long COVID, POTS and MCAS. Across the programme, 423 candidate agents are logged for Long COVID, most of them preliminary; this page isolates the record for one of them.
Evidence table
| Evidence tier | C · Preliminary |
|---|---|
| Evidence score | 29.0 (trials 7.0, literature 17.0, tier 5, approved bonus 0.0) |
| Registered trials | 2 total: 0 recruiting, 0 active / not yet recruiting, 2 completed, 0 other |
| Linked publications | 13 (9 other publications, 2 curated references, 1 systematic review, 1 clinical trial publication) |
| Agent type | Behavioural (Behavioral / Protocol / Exercise, Supplement / Nutraceutical) |
| Development stage (any indication) | Investigational |
| Mechanism / class | Neurological / Autonomic |
| Data sources | OSMF therapeutic agent database, ClinicalTrials.gov, PubMed |
| Also known as | Melatonin |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT06404112 | RECOVER-SLEEP: Platform Protocol, Appendix_B (CPSD) Duke University · 2024 | completed | Phase 2 | 469 |
| NCT06404086 | RECOVER-SLEEP: Platform Protocol Duke University · 2024 | completed | Phase 2 | 830 |
Published literature
- Curated reference (OSMF) Diet and environment: unexplored influences on sleep quality in postural orthostatic tachycardia syndrome (POTS).2026
- Clinical trial publication (PubMed validation search) PubMed record PMID 38908733
- Curated reference PubMed record PMID 42254140
- Review (PubMed validation search) PubMed record PMID 41848128
- Review (PubMed validation search) PubMed record PMID 40534826
- Review (PubMed validation search) PubMed record PMID 38715279
- Review (PubMed validation search) PubMed record PMID 38641847
- Review (PubMed validation search) PubMed record PMID 38299237
- Review (PubMed validation search) PubMed record PMID 37378781
- Review (PubMed validation search) PubMed record PMID 36998709
- Review (PubMed validation search) PubMed record PMID 36829952
- Case report (PubMed validation search) PubMed record PMID 40868937
- Systematic review (PubMed validation search) PubMed record PMID 35422571
Mechanism and notes
Recorded mechanism or class: Neurological / Autonomic.
Clinical notes: Investigational for listed conditions. 2 associated trial(s) and 1 study reference(s) in current data. Review primary sources and consult specialists before use.
Safety: Limited specific safety data in these populations. Review full prescribing information and consult specialist. Many agents used off-label or investigational.
Dosing in studies: See linked studies/trials for reported doses and durations; typical protocols vary widely.
Frequently asked questions
Is Melatonin approved for Long COVID?
Melatonin is tracked by OSMF as an investigational option for Long COVID; no regulator has approved it for this indication, and most post-viral conditions have no approved disease-modifying therapy at all. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Melatonin in clinical trials for Long COVID?
ClinicalTrials.gov lists 2 registered trials linking Melatonin to Long COVID: 2 have completed. The most advanced is Phase 2 (NCT06404086, sponsored by Duke University). It plans or enrolled 830 participants. Registered activity dates to 2024.
What does the evidence show for Melatonin in Long COVID?
Melatonin has both completed registered trials and synthesis-level publications linked to Long COVID. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is C (Preliminary), taken from the OSMF therapeutic agent database, which grades agents by the volume and design of condition-specific evidence rather than by effect size.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-10-07. Page built 2026-10-07.