RECOVER-SLEEP: Platform Protocol

Conditions

• Hypersomnia
• Long COVID
• Long COVID-19
• Sleep Disturbance

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Modafinil — DRUG
  Modafinil is used off-label based on supporting published evidence in major depressive disorder (antidepressant augmentation), multiple sclerosis-related fatigue, Parkinson disease-related excessive daytime sleepiness, and severe cancer-related fatigue (in patients receiving active treatment). Doses up to 400 mg/day, given as a singleMode dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg dose. Study drug administration will total 10 weeks.
• Modafinil Placebo — DRUG
  The placebo will be tooled to look similar to the modafinil tablet, but it will not contain the active ingredient. Modafinil placebo dosing will follow the same titration scheme as modafinil treatment. Unblinded study personnel will manage modafinil and placebo disbursement to maintain blinding among participants and blinded study personnel, including site investigators.
• Solriamfetol — DRUG
  The proposed doses and the schedule of dose escalation are consistent with currently approved FDA labeling for solriamfetol for other disorders of excessive daytime sleepiness. Solriamfetol dosing will total 10 weeks, including 3 weeks for titration and 7 weeks of maintenance. Solriamfetol will be given as a 75 mg tablet (1 or 2 per day) in the morning. The 3-week titration will be facilitated by phone calls between the study team and participants. Titrations in dose will be dependent upon participants' symptoms and tolerance to solriamfetol, with a goal of participants taking the highest dose permitted by symptoms. This dose will be used for the maintenance phase.
• Solriamfetol Placebo — DRUG
  The placebo tablet will be tooled to look similar to the solriamfetol tablet, but it will not contain the active ingredient. Solriamfetol placebo dosing will follow the solriamfetol dosing scheme and goal. Unblinded study personnel will manage solriamfetol and placebo disbursement to maintain blinding among participants and blinded study personnel, including site investigators.
• Melatonin — DRUG
  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.
• Melantonin Placebo — DRUG
  Melatonin placebo dosing will be one placebo tablet once daily consumed 2 hours before the participant's desired bedtime.
• Tailored lighting (TL) Active — DEVICE
  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.
• Tailored lighting (TL) Placebo — DEVICE
  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.

Study Details

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).

Key Dates

Start date

Jul 31, 2024

Status verified

Jan 2026

Primary completion

Dec 31, 2025

Completion

Dec 31, 2025

Study Design

Enrollment

830 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Other: Hypersomnia Arm (Appendix A)
  This is a double-blind, phase 2, randomized, placebo-controlled interventional trial of a wake-promoting drug (modafinil or solriamfetol) to treat hypersomnia, defined by elevated scores (\> 55) on the PROMIS 8a SRI scale, in participants with PASC. Participants will be randomized to study drug or control. Participants who meet the eligibility criteria for modafinil will receive either active modafinil or modafinil-matched control. If modafinil is contraindicated, participants will be assessed for solriamfetol. If participants are eligible for solriamfetol, they will receive either active solriamfetol or solriamfetol-matched control. If solriamfetol is contraindicated, participants will be excluded from Appendix A. Modafinil and solriamfetol will be analyzed as a single wake-promoting drug condition versus control. The intervention duration will be 10 weeks. Anticipated enrollment is 474 participants. Details about the Hypersomnia Appendix are available under NCT06404099.
• Other: Complex PASC related Sleep Disturbances (CPSD) Arm (Appendix B )
  This is a double-blind, phase 2, randomized, placebo-controlled, interventional trial that combines brief education and a tailored sleep timing prescription for CPSD with therapies that modify circadian timing for participants who report poor sleep quality or daytime sleep-related impairment, defined by elevated scores (≥55) on the PROMIS 8b SD scale, in participants with symptoms that occurred or worsened after COVID-19 infection. Interventions involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to 1 of 4 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 BBT-CPSD. It is a 2x2 factorial design schema. The intervention duration will be 8 weeks. Anticipated enrollment for this appendix is 600 participants. Additional details about the CPSD Appendix are available under NCT06404112.

Primary Outcome Measure

Total number of participants enrolled in each Appendix [ Time Frame: 12 months ]

Locations (47)

Find similar trials in Phoenix, AZ

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