RECOVER-SLEEP: Platform Protocol
RECOVER-SLEEP: A Platform Protocol for Evaluation of Interventions for Sleep Disturbances in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
2 other identifiers
interventional
830
1 country
47
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2024
Shorter than P25 for phase_2
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 6, 2024
CompletedFirst Posted
Study publicly available on registry
May 8, 2024
CompletedStudy Start
First participant enrolled
July 31, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2025
CompletedJanuary 22, 2026
January 1, 2026
1.4 years
May 6, 2024
January 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Total number of participants enrolled in each Appendix
Total number of participants enrolled in each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT#.
12 months
Study Arms (2)
Hypersomnia Arm (Appendix A)
OTHERThis 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.
Complex PASC related Sleep Disturbances (CPSD) Arm (Appendix B )
OTHERThis 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.
Interventions
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.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- ≥ 18 years of age at the time of enrollment
- Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization:
- Suspected\* case of SARS-CoV-2 infection - Three options, A through C:
- A. Met the clinical OR epidemiological criteria:
- Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia;
- Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presented with acute respiratory infection with a history of fever or measured fever of ≥ 38°C and cough, with onset within the last 10 days, and required hospitalization; or C. Presented with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
- Probable\* case of SARS-CoV-2 infection, defined as having met the clinical criteria above AND was a contact of a probable or confirmed case or is linked to a COVID-19 cluster; or
- Confirmed case of SARS-CoV-2 infection - Two options, A through B:
- A. Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Met clinical criteria AND/OR epidemiological criteria (See suspected case A), with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
- \* Suspected and probable cases will only be allowed if they occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.
- New/worse sleep problems following a SARS-CoV-2 infection that have persisted for at least 12 weeks and are still present at the time of consent
- PROMIS 8a SRI or 8b SD T Score ≥ 55\*\*
- \*\* Screening with both the PROMIS 8a SRI and 8b SD will occur for the phenotype assessment portion of the protocol.
- Willing and able to provide informed consent, complete the surveys and clinical assessments, and return for all of the necessary follow-up visits
- +1 more criteria
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
- Known pregnancy, breastfeeding, or contemplating pregnancy during the study period
- Untreated sleep apnea (AHI ≥ 15 or severe sleep-related hypoxemia)
- Current night or rotating shift work
- Known history of narcolepsy prior to SARS-CoV-2 infection
- Any non-marijuana illicit drug use within 30 days of informed consent
- Known history of severe mental disorder, such as psychotic disorders and bipolar disorder
- Current or recent use (within the last 14 days) of study intervention or similar intervention to treat the underlying condition, unless a washout period is permitted per appendix\*
- Known allergy/sensitivity or any hypersensitivity to components of the study intervention or control\*
- Known contraindication(s) to study intervention including prohibited concomitant medications and without the ability to safely hold prohibited concomitant medications (see appendices)\*
- Currently receiving/using intervention from another clinical trial that could impact or mask treatment effect; refer to MOP for details
- Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
- (\*)If only one study intervention appendix is open at the time of enrollment. If multiple study intervention appendices are open, a participant may be excluded from any study intervention appendix based on contraindications listed in the study intervention appendix, current use of study intervention, or known allergy/sensitivity/hypersensitivity yet remain eligible for the remaining study intervention appendices.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Duke Universitylead
Study Sites (47)
Banner University Medical Center Phoenix
Phoenix, Arizona, 85006, United States
University of Arizona Banner Medical Center
Tucson, Arizona, 85719, United States
The Southern Arizona VA Health Care System
Tucson, Arizona, 85723, United States
Stanford University
Palo Alto, California, 94304, United States
University of California San Francisco General Hospital
San Francisco, California, 94143, United States
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045, United States
Denver Health and Hospital Authority
Denver, Colorado, 80204, United States
Howard University Hospital
Washington D.C., District of Columbia, 20060, United States
University of Florida College of Medicine Jacksonville
Jacksonville, Florida, 32209, United States
Lakeland Regional Medical Center
Lakeland, Florida, 33805, United States
Grady Memorial Hospital
Atlanta, Georgia, 30303, United States
Morehouse School of Medicine
Atlanta, Georgia, 30310, United States
Emory University
Atlanta, Georgia, 30322, United States
Atlanta VA Medical Center
Decatur, Georgia, 30030, United States
Emory Hope Clinic
Decatur, Georgia, 30030, United States
Northwestern Memorial Hospital
Chicago, Illinois, 60611, United States
Cook County Health Specialty Care Center
Chicago, Illinois, 60612, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
NorthShore Medical Group
Evanston, Illinois, 60201, United States
Saint Francis Medical Center
Peoria, Illinois, 61606, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224, United States
Jadestone Clinical Research, LLC
Silver Spring, Maryland, 20904, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Brigham and Womens Hospital
Boston, Massachusetts, 02115, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Beth Israel Deaconess Med. Ctr.
Boston, Massachusetts, 02215, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655, United States
Rutgers University - Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901, United States
University of New Mexico
Albuquerque, New Mexico, 87102, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
East Carolina University
Greenville, North Carolina, 27834, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45220, United States
University Hospitals of Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Southwest Family Medicine Associates
Dallas, Texas, 75235, United States
Houston Methodist Hospital
Houston, Texas, 77030, United States
University of Texas Health Science Center at Houston
Houston, Texas, 77030, United States
New Dawn Wellness and Medical Research Center
Houston, Texas, 77082, United States
University of Virginia Health System
Charlottesville, Virginia, 22908, United States
Evergreen Hospital Medical Center
Kirkland, Washington, 98034, United States
University Physicians and Surgeons (DBA Marshall Health)
Huntington, West Virginia, 25701, United States
West Virginia Clinical and Translational Science Institute
Morgantown, West Virginia, 26506, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Christina Barkauskas, MD
Duke Clinical Research Institute
- STUDY CHAIR
Susan Redline, MD MPH
Brigham and Women's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Double blind
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 6, 2024
First Posted
May 8, 2024
Study Start
July 31, 2024
Primary Completion
December 31, 2025
Study Completion
December 31, 2025
Last Updated
January 22, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share
The summary of results will be shared on the study website: https://recovercovid.org/