The platform protocol is designed to be flexible so that it is suitable for a range ofstudy settings and intervention types. Therefore, the platform protocol provides ageneral protocol structure that can be shared by multiple interventions and allowscomparative analysis across the interventions. For example, objectives, measures, andendpoints are generalized in the platform protocol, but intervention-specific featuresare detailed in separate appendices.This platform protocol is a prospective, multi-center, multi-arm, randomized controlledplatform trial evaluating potential interventions for PASC-mediated sleep disturbances.The hypothesis is that symptoms of sleep and circadian disorders that emerge in patientswith PASC can be improved by phenotype-targeted interventions. Specific sleep andcircadian disorders addressed in this protocol include sleep-related daytime impairment(referred to as hypersomnia) and complex PASC-related sleep disturbance (reflectingsymptoms of insomnia and sleep-wake rhythm disturbance).
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.
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: 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
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.
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.
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
All sites listed under NCT06404086
Durham, North Carolina, United States
Jaelyn R Linski, BA, CCRC
919-668-8060
recoverresearch@duke.edu
Barrie L Harper, BSMT (ASCP) PMP
recoverresearch@duke.edu