RECOVER-SLEEP: Platform Protocol, Appendix_A (Hypersomnia)

Long COVID Clinical Trial

Official title:

RECOVER-SLEEP: A Platform Protocol for Evaluation of Interventions for Sleep Disturbances in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06404099
• Other study ID #: Pro00112484_A
• Secondary ID: OTA-21-015G
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: November 2025

Study information

• Verified date: May 2024
• Source: Duke University
• Contact: Jaelyn R Linski, BA, CCRC
• Phone: 919-668-8060
• Email: recoverresearch[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 474
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disorders of Excessive Somnolence
• Hypersomnia
• Long COVID
• Long COVID-19

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 60 being 1 standard deviation above population mean. Higher scores indicate greater sleep-related impairment.	Baseline, End of Intervention (Day 77)
Secondary	Change in total score of the PROMIS 8b SD to assess sleep disturbance	The PROMIS 8b SD form includes a total of 8 items that ask participants to reflect on their sleep over the past 7 days with one question rated very poor to very good and the remaining questions rated not at all to very much. T-Scores range from 0 to 100, with > 60 1 SD above population mean.	Baseline, End of Intervention (Day 77)
Secondary	Change in PROMIS 10a Fatigue score	The PROMIS 10a Fatigue is a 10-item questionnaire that assesses a participant's fatigue on a scale of 1 (not at all fatigued) to 5 (very much).	Baseline, End of Intervention (Day 77)
Secondary	Change in an objective neurocognitive battery score		Baseline, End of Intervention (Day 77)
Secondary	Change in ECog2 measure	Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure measure the participant's perceived capacity to perform activities related to cognitive function, which could impact major activities of daily living and independence. It has been used for patients with mild cognitive impairment, Alzheimer's Disease, and dementia. It takes 5 minutes to complete.	Baseline, End of Intervention (Day 77)
Secondary	Change in PASC Symptom Questionnaire responses	Participants will be asked to complete a questionnaire that asks about the presence of PASC symptoms at Baseline and at follow-up visits. This questionnaire includes symptoms that have been associated with PASC.	Baseline, End of Intervention (Day 77)
Secondary	Change in total score on the Insomnia Severity Index (ISI)	The ISI is a 7-item, self-report questionnaire that assesses the nature, severity, and impact of insomnia, on a 5-point Likert scale (eg, 0 = not at all, 4 = extremely; scores: from 0 to 28). The ISI asks patients to recall their insomnia symptoms over the past 2 weeks.	Baseline, End of Intervention (Day 77)
Secondary	Change in within-person variability (over a 7-day period) in sleep onset time, assessed by sleep diary	Sleep onset time will be assessed by sleep diary	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) nocturnal sleep duration, assessed by sleep diary	Nocturnal sleep duration will be assessed by sleep diary	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) 24-hour sleep duration, assessed by sleep diary	24-hour sleep duration will be assessed by sleep diary	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) sleep midpoint, assessed by sleep diary	Sleep midpoint is the time half way between start and end of sleep, as assessed by sleep diary	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) nocturnal sleep duration, assessed by activity tracker	Nocturnal sleep duration will be assessed by activity tracker	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) 24-hour sleep duration, assessed by activity tracker	24-hour sleep duration will be assessed by activity tracker	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) sleep efficiency, assessed by activity tracker	Sleep Efficiency is the percentage of the sleep period spent asleep, as measured by activity tracker	Baseline, End of Intervention (Day 77)
Secondary	Change in average (over a 7-day period) sleep midpoint, assessed by activity tracker	Sleep midpoint is the time half way between start and end of sleep, as assessed by sleep diary	Baseline, End of Intervention (Day 77)

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