Hypersomnia, Long COVID, Long COVID-19
Conditions
Keywords
PASC
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).
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.
Interventions
DRUGModafinil
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.
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.
DRUGSolriamfetol
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.
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.
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in total score of the PROMIS 8a SRI to assess sleep-related impairment | Baseline, End of Intervention (Day 77) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in total score of the PROMIS 8b SD to assess sleep disturbance | Baseline, End of Intervention (Day 77) | 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 \> 55 1 SD above population mean. |
| Change in PROMIS 10a Fatigue score | Baseline, End of Intervention (Day 77) | 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). |
| Change in an objective neurocognitive battery score | Baseline, End of Intervention (Day 77) | — |
| Change in ECog2 measure | Baseline, End of Intervention (Day 77) | 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. |
| Change in PASC Symptom Questionnaire responses | Baseline, End of Intervention (Day 77) | 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. |
| Change in total score on the Insomnia Severity Index (ISI) | Baseline, End of Intervention (Day 77) | 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. |
| Change in within-person variability (over a 7-day period) in sleep onset time, assessed by sleep diary | Baseline, End of Intervention (Day 77) | Sleep onset time will be assessed by sleep diary |
| Change in average (over a 7-day period) nocturnal sleep duration, assessed by sleep diary | Baseline, End of Intervention (Day 77) | Nocturnal sleep duration will be assessed by sleep diary |
| Change in average (over a 7-day period) 24-hour sleep duration, assessed by sleep diary | Baseline, End of Intervention (Day 77) | 24-hour sleep duration will be assessed by sleep diary |
| Change in average (over a 7-day period) sleep midpoint, assessed by sleep diary | Baseline, End of Intervention (Day 77) | Sleep midpoint is the time half way between start and end of sleep, as assessed by sleep diary |
| Change in average (over a 7-day period) nocturnal sleep duration, assessed by activity tracker | Baseline, End of Intervention (Day 77) | Nocturnal sleep duration will be assessed by activity tracker |
| Change in average (over a 7-day period) 24-hour sleep duration, assessed by activity tracker | Baseline, End of Intervention (Day 77) | 24-hour sleep duration will be assessed by activity tracker |
| Change in average (over a 7-day period) sleep efficiency, assessed by activity tracker | Baseline, End of Intervention (Day 77) | Sleep Efficiency is the percentage of the sleep period spent asleep, as measured by activity tracker |
| Change in average (over a 7-day period) sleep midpoint, assessed by activity tracker | Baseline, End of Intervention (Day 77) | Sleep midpoint is the time half way between start and end of sleep, as assessed by sleep diary |
Countries
United States
Contacts
STUDY_CHAIRChristina Barkauskas, MD
Duke Clinical Research Institute
STUDY_CHAIRSusan Redline, MD MPH
Brigham and Women's Hospital
Outcome results
None listed