RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)

Duke University

Status and phase: Active, not recruiting; Phase 2

Conditions: Long COVID; Long COVID-19; Hypersomnia

Treatments: Drug: Solriamfetol Placebo; Drug: Modafinil Placebo; Drug: Modafinil; Drug: Solriamfetol

Study type: Interventional

Funder types: Other

Identifiers

NCT06404099

OTA-21-015G (Other Grant/Funding Number)

Pro00112484_A

Details and patient eligibility

About

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).

Full 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.

Enrollment: 361 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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361 participants in 2 patient groups, including a placebo group

Wake-promoting drug: Modafinil or solriamfetol

Active Comparator group

Description:

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.

Treatment:

Drug: Solriamfetol

Drug: Modafinil

Modafinil-matched placebo or solriamfetol-matched placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Modafinil Placebo

Drug: Solriamfetol Placebo