RECOVER-SLEEP: Platform Protocol
Purpose
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).
Conditions
- Long COVID
- Long COVID-19
- Hypersomnia
- Sleep Disturbance
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. ≥ 18 years of age at the time of enrollment 2. 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: 1. 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; 2. 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. 3. 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 4. 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. 5. Willing and able to provide informed consent, complete the surveys and clinical assessments, and return for all of the necessary follow-up visits 6. Adequate method of birth control for participants of child-bearing potential
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this study: 1. Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent 2. Known pregnancy, breastfeeding, or contemplating pregnancy during the study period 3. Untreated sleep apnea (AHI ≥ 15 or severe sleep-related hypoxemia) 4. Current night or rotating shift work 5. Known history of narcolepsy prior to SARS-CoV-2 infection 6. Any non-marijuana illicit drug use within 30 days of informed consent 7. Known history of severe mental disorder, such as psychotic disorders and bipolar disorder 8. 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* 9. Known allergy/sensitivity or any hypersensitivity to components of the study intervention or control* 10. Known contraindication(s) to study intervention including prohibited concomitant medications and without the ability to safely hold prohibited concomitant medications (see appendices)* 11. Currently receiving/using intervention from another clinical trial that could impact or mask treatment effect; refer to MOP for details 12. 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- This platform protocol is designed to allocate participants into an intervention appendix based on their symptoms of sleep disturbance. Within the appendix, participants will be randomly assigned based on the appendix study design. Site investigators and personnel will be informed as to which study intervention appendix participants are assigned, but they will be blinded to whether participants are receiving the active study intervention or control, when possible. Similarly, participants will be blinded to active intervention or control, when possible. Randomization will be stratified by the study site; other stratification factors may be considered per appendix.
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- Double blind
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
Recruiting Locations
Tucson 5318313, Arizona 5551752 85719
Tucson 5318313, Arizona 5551752 85723
Adnan Abbasi, MD
Palo Alto 5380748, California 5332921 94304
San Francisco 5391959, California 5332921 94143
Aric Prather, MD
Aurora 5412347, Colorado 5417618 80045
Sarah Jolley, MD
Denver 5419384, Colorado 5417618 80204
Edward Gardner, MD
Washington D.C. 4140963, District of Columbia 4138106 20060
Peter Whitesell
Jacksonville 4160021, Florida 4155751 32209
Carmen Isache, MD
Lakeland 4161438, Florida 4155751 33805
Debra Seoane, MD
Atlanta 4180439, Georgia 4197000 30303
Jenny Han, MD
Atlanta 4180439, Georgia 4197000 30310
Priscilla Igho-Pemu
Atlanta 4180439, Georgia 4197000 30322
Decatur 4191124, Georgia 4197000 30030
Barry Fields, MD
Decatur 4191124, Georgia 4197000 30030
Wiley Zanthia, MD
Chicago 4887398, Illinois 4896861 60611
Phyllis Zee, MD
Chicago 4887398, Illinois 4896861 60612
James Moy, MD
Chicago 4887398, Illinois 4896861 60612
Bharati Prasad, MD
Evanston 4891382, Illinois 4896861 60201
Peoria 4905687, Illinois 4896861 61606
Patrick Whitten, MD
Kansas City 4273837, Kansas 4273857 66160
Damien Stevens, MD
Lexington 4297983, Kentucky 6254925 40536
Christopher Simmons, MD
Baltimore 4347778, Maryland 4361885 21224
Silver Spring 4369596, Maryland 4361885 20904
Jonathan Cohen, MD
Boston 4930956, Massachusetts 6254926 02111
Boston 4930956, Massachusetts 6254926 02114
Boston 4930956, Massachusetts 6254926 02115
Daniel Gottlieb, MD
Boston 4930956, Massachusetts 6254926 02118
Sanford Auerbach, MD
Boston 4930956, Massachusetts 6254926 02215
Janet Mullington, MD
Worcester 4956184, Massachusetts 6254926 01655
Jennifer Wang, MD
New Brunswick 5101717, New Jersey 5101760 08901
Sabiha Hussain, MD
Albuquerque 5454711, New Mexico 5481136 87102
New York 5128581, New York 5128638 10029
Vaishnavi Kundel, MD
Greenville 4469160, North Carolina 4482348 27834
Paul Bolin, MD
Cincinnati 4508722, Ohio 5165418 45220
Ann Romaker, MD
Cleveland 5150529, Ohio 5165418 44106
Kingman Strohl, MD
Portland 5746545, Oregon 5744337 97239
Hope Aluko, MD
Dallas 4684888, Texas 4736286 75235
Houston 4699066, Texas 4736286 77030
Eleftherios Mylonakis, MD
Houston 4699066, Texas 4736286 77030
Reeba Matthew, MD
Houston 4699066, Texas 4736286 77082
Adanna Ukazu, MD
Charlottesville 4752031, Virginia 6254928 22908
Alexandra Kadl, MD
Kirkland 5799841, Washington 5815135 98034
Pinky Agarwal, MD
Huntington 4809537, West Virginia 4826850 25701
Imran Khawaja, MD
Morgantown 4815352, West Virginia 4826850 26506
Sunil Sharma, MD
Milwaukee 5263045, Wisconsin 5279468 53226
More Details
- NCT ID
- NCT06404086
- Status
- Recruiting
- Sponsor
- Duke University
Detailed Description
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.