Clinical trial NCT06404099: RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)
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
Keywords: PASC
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2024-05-08
Enrollment: 474
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:

• See NCT06404086 for RECOVER-SLEEP: Platform Protocol level inclusion criteria which applies to this appendix

Exclusion Criteria:

• See NCT06404086 for RECOVER-SLEEP: Platform Protocol level exclusion criteria which applies to this appendix (or sub-study)

Additional Appendix A (Hypersomnia) Level Exclusion Criteria:

1. Self-reported sleep duration \<6 hours per night
2. Poorly controlled hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg)
3. Moderate to severe hepatic impairment (ie, Child-Pugh class B or C)\*
4. Known estimated glomerular filtration rate \<30 mL/min/1.73 m2 and/or chronic dialysis\*
5. Recent myocardial infarction (\<1 year), unstable angina, serious cardiac arrhythmias, or other serious heart problems, at the discretion of the investigator
6. Current use of stimulant or wake-promoting medications, unless a washout is permitted
7. Regular use of prescribed hypnotics for sleep (≥3 times per week); washout period is permitted.

   * characterized by the screening labs: coagulation panel and CMP w/LFTs

MODAFINIL EXCLUSION CRITERIA

1. Modafinil can affect drug metabolism given its effect on enzymes such as CYP3A4 and CYP2C19. To assess for drug interactions, investigators should use the Lexicomp Drug Interactions System that is available at most institutions.

   o If the search yields "D" - Consider Modifying Therapy or "X" - Avoid Combination, then the ACTION is to exclude the potential participant.

   An important example of this is steroid hormonal contraceptives.
   * If the search yields "C" - Monitor Therapy, then discuss with site PIs on a case-by-case basis.
   * If the search yields "A" - No Known Interaction or "B" - No Action Needed, then proceed to screen/include the potential participant.
2. Known severe left ventricular hypertrophy, mitral valve prolapse

SOLRIAMFETOL EXCLUSION CRITERIA

1. Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days
2. Current use of dopaminergic drugs

Primary outcomes:
measure: Change in total score of the PROMIS 8a SRI to assess sleep-related impairment
timeFrame: Baseline, End of Intervention (Day 77)
Secondary outcomes:
measure: Change in total score of the PROMIS 8b SD to assess sleep disturbance
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in PROMIS 10a Fatigue score
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in an objective neurocognitive battery score
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in ECog2 measure
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in PASC Symptom Questionnaire responses
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in total score on the Insomnia Severity Index (ISI)
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in within-person variability (over a 7-day period) in sleep onset time, assessed by sleep diary
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) nocturnal sleep duration, assessed by sleep diary
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) 24-hour sleep duration, assessed by sleep diary
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) sleep midpoint, assessed by sleep diary
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) nocturnal sleep duration, assessed by activity tracker
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) 24-hour sleep duration, assessed by activity tracker
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) sleep efficiency, assessed by activity tracker
timeFrame: Baseline, End of Intervention (Day 77)
measure: Change in average (over a 7-day period) sleep midpoint, assessed by activity tracker
timeFrame: Baseline, End of Intervention (Day 77)
Other outcomes:
Locations:
city: Durham
country: United States
facility: All sites listed under NCT06404086
state: North Carolina
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: