Clinical trial NCT06404086: RECOVER-SLEEP: Platform Protocol
Official title: RECOVER-SLEEP: A Platform Protocol for Evaluation of Interventions for Sleep Disturbances in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Long COVID
Long COVID-19
Hypersomnia
Sleep Disturbance
Keywords: PASC
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2024-05-08
Enrollment: 1074
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total number of participants enrolled in each Appendix
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center Phoenix
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Banner Medical Center
state: Arizona
city: San Francisco
country: United States
facility: University of California San Francisco General Hospital
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida College of Medicine Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Decatur
country: United States
facility: Emory Hope Clinic
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Cook County Health Specialty Care Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Evanston
country: United States
facility: NorthShore Medical Group
state: Illinois
city: Peoria
country: United States
facility: Saint Francis Medical Center
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Silver Spring
country: United States
facility: Jadestone Clinical Research, LLC
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr.
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers University - Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Dallas
country: United States
facility: Southwest Family Medicine Associates
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: New Dawn Wellness and Medical Research Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Huntington
country: United States
facility: University Physicians and Surgeons (DBA Marshall Health)
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia Clinical and Translational Science Institute
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Duke Clinical Research Institute
name: Christina Barkauskas, MD
role: STUDY_CHAIR
affiliation: Brigham and Women's Hospital
name: Susan Redline, MD MPH
role: STUDY_CHAIR
References: