RECOVER-SLEEP: Platform Protocol, Appendix_B (CPSD)

NCT06404112 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: Pro00112484_BOTA-21-015G
• Study Type: interventional
• Target: 470
• Locations: 1 country
• Sites: 1

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).

Conditions

Sleep Disturbance; Long COVID; Long COVID-19

Keywords

PASC; Sleep Disturbances

Outcome Measures

Primary Outcomes (2)

• 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 a score of 55 being 1 standard deviation above population mean. Higher scores indicate more sleep disturbance.

  Baseline, End of Intervention (Day 63)

• Change in sleep onset variability, assessed using a wearable device

  A wearable device will be used as an objective measure to assess sleep onset variability assessed for 7 days before randomization and 7 days before EOI

  Baseline, End of Intervention (Day 63)

Secondary Outcomes (14)

• Change in total score of the PROMIS 8a SRI to assess sleep-related impairment

  Baseline, End of Intervention (Day 63)

• Change in PROMIS 10a Fatigue score

  Baseline, End of Intervention (Day 63)

• Change in an objective neurocognitive battery score

  Baseline, End of Intervention (Day 63)

• Change in ECog2 measure

  Baseline, End of Intervention (Day 63)

• Change in PASC Symptom Questionnaire responses

  Baseline, End of Intervention (Day 63)

Study Arms (4)

Active TL + Oral Melatonin

ACTIVE COMPARATOR

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Drug: Melatonin; Device: Tailored lighting (TL) Active

Active TL + Placebo Melatonin

ACTIVE COMPARATOR

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Drug: Melantonin Placebo; Device: Tailored lighting (TL) Active

Placebo TL + Oral Melatonin

ACTIVE COMPARATOR

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Drug: Melatonin; Device: Tailored lighting (TL) Placebo

Placebo TL + Placebo Melatonin

PLACEBO COMPARATOR

The Complex PASC-Related Sleep Disturbances (CPSD) Appendix B combines brief education and a tailored sleep timing prescription for CPSD (referred to as RESET-PASC) with therapies that modify circadian timing for participants who report poor sleep quality. The intervention therapies involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to one of four groups: (a) active TL + oral melatonin, (b) active TL + placebo melatonin, (c) placebo TL + oral melatonin, and (d) placebo TL + placebo melatonin. All groups will receive RESET-PASC. The intervention duration will be 8 weeks.

Drug: Melantonin Placebo; Device: Tailored lighting (TL) Placebo

Interventions

Melatonin DRUG

Melatonin dosing will be one tablet of 3 mg immediate release daily consumed 2 hours before the participant's desired bedtime, which is defined as the time at which the participant tries to fall asleep.

Active TL + Oral Melatonin; Placebo TL + Oral Melatonin

Melantonin Placebo DRUG

Melatonin placebo dosing will be one placebo tablet once daily consumed 2 hours before the participant's desired bedtime.

Active TL + Placebo Melatonin; Placebo TL + Placebo Melatonin

Tailored lighting (TL) Active DEVICE

TL will be delivered similarly to both active and placebo groups, but the circadian stimulus (the amount of light) will be different, albeit practically unidentifiable to participants.

Active TL + Oral Melatonin; Active TL + Placebo Melatonin

Tailored lighting (TL) Placebo DEVICE

TL will be delivered similarly to both active and placebo groups, but the circadian stimulus (the amount of light) will be different, albeit practically unidentifiable to participants.

Placebo TL + Oral Melatonin; Placebo TL + Placebo Melatonin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Severe visual impairments affecting sensitivity or ability to respond to light
• Severe photosensitivity dermatitis
• Severe progressive retinal disease, eg, macular degeneration
• Permanently dilated pupil, eg, following certain cataract surgeries
• Unwilling to remove or not wear blue-light-blocking glasses during TL dosing
• \. Sleep medication, if not willing to washout for 4 weeks.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

All sites listed under NCT06404086

Durham, North Carolina, 27710, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Parasomnias

Interventions

Melatonin

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Christina Barkauskas, MD

  Duke Clinical Research Institute

  STUDY CHAIR

• Susan Redline, MD MPH

  Brigham and Women's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: May 8, 2024
• Study Start: July 31, 2024
• Primary Completion: March 3, 2026
• Study Completion: April 3, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)