RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

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

ArmDescriptionAssigned Intervention
Active Comparator
Wake-promoting drug: Modafinil or solriamfetol 		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
    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.
  • Drug: Solriamfetol
    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.
Placebo Comparator
Modafinil-matched placebo or solriamfetol-matched placebo 		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
    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.
  • Drug: Solriamfetol Placebo
    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.

Recruiting Locations

All sites listed under NCT06404086
Durham, North Carolina 27710

More Details

NCT ID
NCT06404099
Status
Recruiting
Sponsor
Duke University

Study Contact

Jaelyn R Linski, BA, CCRC
919-668-8060
recoverresearch@duke.edu

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.