A Phase 2 interventional study of Melatonin and Melantonin Placebo in Long COVID, Long COVID-19 and Sleep Disturbance, sponsored by Duke University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by Duke University · Phase 2, Interventional, and Treatment
The platform protocol is designed to be flexible so that it is suitable for a range of study settings and intervention types. Therefore, the platform protocol provides a general protocol structure that can be shared by multiple interventions and allows comparative analysis across the interventions. For example, objectives, measures, and endpoints are generalized in the platform protocol, but intervention-specific features are detailed in separate appendices.
This platform protocol is a prospective, multi-center, multi-arm, randomized controlled platform trial evaluating potential interventions for PASC-mediated sleep disturbances. The hypothesis is that symptoms of sleep and circadian disorders that emerge in patients with PASC can be improved by phenotype-targeted interventions. Specific sleep and circadian disorders addressed in this protocol include sleep-related daytime impairment (referred to as hypersomnia) and complex PASC-related sleep disturbance (reflecting symptoms of insomnia and sleep-wake rhythm disturbance).
Interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix.
After completing Baseline assessments, participants will be randomized to an intervention group, which is based on their sleep phenotype, or into a placebo/control group.
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Exclusion Criteria:
Additional Appendix B (CPSD) Level Inclusion Criteria:
The following additional exclusion criteria are to be considered together for determining eligibility. They are separated here by TL and melatonin only for presentation. RESET-PASC presents no additional exclusions.
TAILORED LIGHTING EXCLUSION CRITERIA
MELATONIN EXCLUSION CRITERIA
1. Sleep medication, if not willing to washout for 4 weeks.
The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.
Drug: Melatonin · Device: Tailored lighting (TL) Active
The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.
Drug: Melantonin Placebo · Device: Tailored lighting (TL) Active
The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.
Drug: Melatonin · Device: Tailored lighting (TL) Placebo
The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.
Drug: Melantonin Placebo · Device: Tailored lighting (TL) Placebo
Melatonin dosing will be one tablet of 3 mg immediate release daily consumed 2 hours before the participant's desired bedtime, which is defined as the time at which the participant tries to fall asleep.
Melatonin placebo dosing will be one placebo tablet once daily consumed 2 hours before the participant's desired bedtime.
TL will be delivered similarly to both active and placebo groups, but the circadian stimulus (the amount of light) will be different, albeit practically unidentifiable to participants.
TL will be delivered similarly to both active and placebo groups, but the circadian stimulus (the amount of light) will be different, albeit practically unidentifiable to participants.
Change in total score of the PROMIS 8b SD to assess sleep disturbance
The PROMIS 8b SD form includes a total of 8 items that ask participants to reflect on their sleep over the past 7 days with one question rated very poor to very good and the remaining questions rated not at all to very much. T-Scores range from 0 to 100, with a score of 55 being 1 standard deviation above population mean. Higher scores indicate more sleep disturbance.
Time frame: Baseline, End of Intervention (Day 63)
Change in sleep onset variability, assessed using a wearable device
A wearable device will be used as an objective measure to assess sleep onset variability assessed for 7 days before randomization and 7 days before EOI
Time frame: Baseline, End of Intervention (Day 63)
Change in total score of the PROMIS 8a SRI to assess sleep-related impairment
The PROMIS 8a SRI form includes a total of 8 items that ask participants to reflect on their sleep-related daytime impairment over the past 7 days with questions rated not at all to very much. T-Scores range from 0 to 100, with \> 55 1 SD above population mean.
Time frame: Baseline, End of Intervention (Day 63)
Change in PROMIS 10a Fatigue score
The PROMIS 10a Fatigue is a 10-item questionnaire that assesses a participant's fatigue on a scale of 1 (not at all fatigued) to 5 (very much).
Time frame: Baseline, End of Intervention (Day 63)
Change in an objective neurocognitive battery score
Time frame: Baseline, End of Intervention (Day 63)
Change in ECog2 measure
Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure measure the participant's perceived capacity to perform activities related to cognitive function, which could impact major activities of daily living and independence. It has been used for patients with mild cognitive impairment, Alzheimer's Disease, and dementia. It takes 5 minutes to complete.
Time frame: Baseline, End of Intervention (Day 63)
Change in PASC Symptom Questionnaire responses
Participants will be asked to complete a questionnaire that asks about the presence of PASC symptoms at Baseline and at follow-up visits. This questionnaire includes symptoms that have been associated with PASC.
Time frame: Baseline, End of Intervention (Day 63)
Change in total score from ISI (Insomnia Severity Index)
The ISI is a 7-item, self-report questionnaire that assesses the nature, severity, and impact of insomnia, on a 5-point Likert scale (eg, 0 = not at all, 4 = extremely; scores: from 0 to 28). The ISI asks patients to recall their insomnia symptoms over the past 2 weeks.
Time frame: Baseline, End of Intervention (Day 63)
Change in within-person variability (over a 7-day period) in sleep onset time, assessed by sleep diary
Sleep onset time will be assessed by sleep diary
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) nocturnal sleep duration, assessed by sleep diary
Nocturnal sleep duration will be assessed by sleep diary
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) 24-hour sleep duration, assessed by sleep diary
24-hour sleep duration will be assessed by sleep diary
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) sleep midpoint, assessed by sleep diary
Sleep midpoint is the time half way between start and end of sleep, as assessed by sleep diary
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) nocturnal sleep duration, assessed by activity tracker
Nocturnal sleep duration will be assessed by activity tracker
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) 24-hour sleep duration, assessed by activity tracker
24-hour sleep duration will be assessed by activity tracker
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) sleep efficiency, assessed by activity tracker
Sleep Efficiency is the percentage of the sleep period spent asleep, as measured by activity tracker
Time frame: Baseline, End of Intervention (Day 63)
Change in average (over a 7-day period) sleep midpoint, assessed by activity tracker
Sleep midpoint is the time half way between start and end of sleep, as assessed by sleep diary
Time frame: Baseline, End of Intervention (Day 63)
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Plan to share: No — The summary of results will be shared on the study website: https://recovercovid.org/
This study is completed, as verified in Jan 2026. You cannot join it, but the record below documents what was studied.
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