RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)

NCT06404099 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro00112484_AOTA-21-015G
• Study Type: interventional
• Target: 361
• Locations: 1 country
• Sites: 1

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).

Conditions

Long COVID; Long COVID-19; Hypersomnia

Keywords

PASC

Outcome Measures

Primary Outcomes (1)

• Change in total score of the PROMIS 8a SRI to assess sleep-related impairment

  The PROMIS 8a SRI form includes a total of 8 items that ask participants to reflect on their sleep-related daytime impairment over the past 7 days with questions rated not at all to very much. T-Scores range from 0 to 100, with a score of 55 being 1 standard deviation above population mean. Higher scores indicate greater sleep-related impairment.

  Baseline, End of Intervention (Day 77)

Secondary Outcomes (14)

• Change in total score of the PROMIS 8b SD to assess sleep disturbance

  Baseline, End of Intervention (Day 77)

• Change in PROMIS 10a Fatigue score

  Baseline, End of Intervention (Day 77)

• Change in an objective neurocognitive battery score

  Baseline, End of Intervention (Day 77)

• Change in ECog2 measure

  Baseline, End of Intervention (Day 77)

• Change in PASC Symptom Questionnaire responses

  Baseline, End of Intervention (Day 77)

Study Arms (2)

Wake-promoting drug: Modafinil or solriamfetol

ACTIVE COMPARATOR

Participants in Appendix A will be randomized to study drug or control. Participants who meet the eligibility criteria for modafinil will receive either active modafinil or the modafinil-matched control. If modafinil is contraindicated for any reason, participants will be assessed for their ability to take solriamfetol. If participants are eligible for solriamfetol, they will receive either active solriamfetol or the 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.

Drug: Modafinil; Drug: Solriamfetol

Modafinil-matched placebo or solriamfetol-matched placebo

PLACEBO COMPARATOR

Participants in Appendix A will be randomized to study drug or control. Participants who meet the eligibility criteria for modafinil will receive either active modafinil or the modafinil-matched control. If modafinil is contraindicated for any reason, participants will be assessed for their ability to take solriamfetol. If participants are eligible for solriamfetol, they will receive either active solriamfetol or the 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.

Drug: Modafinil Placebo; Drug: Solriamfetol Placebo

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.

Wake-promoting drug: Modafinil or solriamfetol

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.

Modafinil-matched placebo or solriamfetol-matched placebo

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.

Wake-promoting drug: Modafinil or solriamfetol

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.

Modafinil-matched placebo or solriamfetol-matched placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Self-reported sleep duration \<6 hours per night
• Poorly controlled hypertension (systolic blood pressure ≥140 or diastolic blood pressure ≥90 mmHg)
• Moderate to severe hepatic impairment (ie, Child-Pugh class B or C)\*
• Known estimated glomerular filtration rate \<30 mL/min/1.73 m2 and/or chronic dialysis\*
• Recent myocardial infarction (\<1 year), unstable angina, serious cardiac arrhythmias, or other serious heart problems, at the discretion of the investigator
• Current use of stimulant or wake-promoting medications, unless a washout is permitted
• 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 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.
• Known severe left ventricular hypertrophy, mitral valve prolapse
• Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

All sites listed under NCT06404086

Durham, North Carolina, 27710, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Disorders of Excessive Somnolence

Interventions

Modafinil; solriamfetol

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Christina Barkauskas, MD

  Duke Clinical Research Institute

  STUDY CHAIR

• Susan Redline, MD MPH

  Brigham and Women's Hospital

  STUDY CHAIR

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

Model Details: 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.

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: May 8, 2024
• Study Start: August 12, 2024
• Primary Completion: March 18, 2026
• Study Completion: April 15, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)