RECOVER-SLEEP: Platform Protocol

Duke University

Status and phase: Enrolling; Phase 2

Conditions: Long COVID; Long COVID-19; Sleep Disturbance; Hypersomnia

Treatments: Device: Tailored lighting (TL) Active; Drug: Solriamfetol Placebo; Drug: Modafinil Placebo; Device: Tailored lighting (TL) Placebo; Drug: Modafinil; Drug: Melantonin Placebo; Drug: Melatonin; Drug: Solriamfetol

Study type: Interventional

Funder types: Other

Identifiers

NCT06404086

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

Pro00112484

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: 1,074 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. ≥ 18 years of age at the time of enrollment

2. Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization:

   Suspected* case of SARS-CoV-2 infection - Three options, A through C:

   A. Met the clinical OR epidemiological criteria:

   1. Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia;
   2. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presented with acute respiratory infection with a history of fever or measured fever of ≥ 38°C and cough, with onset within the last 10 days, and required hospitalization; or C. Presented with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

   Probable* case of SARS-CoV-2 infection, defined as having met the clinical criteria above AND was a contact of a probable or confirmed case or is linked to a COVID-19 cluster; or

   Confirmed case of SARS-CoV-2 infection - Two options, A through B:

   A. Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Met clinical criteria AND/OR epidemiological criteria (See suspected case A), with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

   * Suspected and probable cases will only be allowed if they occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.

3. New/worse sleep problems following a SARS-CoV-2 infection that have persisted for at least 12 weeks and are still present at the time of consent

4. PROMIS 8a SRI or 8b SD T Score ≥ 55**

   ** Screening with both the PROMIS 8a SRI and 8b SD will occur for the phenotype assessment portion of the protocol.

5. Willing and able to provide informed consent, complete the surveys and clinical assessments, and return for all of the necessary follow-up visits

6. Adequate method of birth control for participants of child-bearing potential

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
2. Known pregnancy, breastfeeding, or contemplating pregnancy during the study period
3. Untreated sleep apnea (AHI ≥ 15 or severe sleep-related hypoxemia)
4. Current night or rotating shift work
5. Known history of narcolepsy prior to SARS-CoV-2 infection
6. Any non-marijuana illicit drug use within 30 days of informed consent
7. Known history of severe mental disorder, such as psychotic disorders and bipolar disorder
8. Current or recent use (within the last 14 days) of study intervention or similar intervention to treat the underlying condition, unless a washout period is permitted per appendix*
9. Known allergy/sensitivity or any hypersensitivity to components of the study intervention or control*
10. Known contraindication(s) to study intervention including prohibited concomitant medications and without the ability to safely hold prohibited concomitant medications (see appendices)*
11. Currently receiving/using intervention from another clinical trial that could impact or mask treatment effect; refer to MOP for details
12. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study

(*)If only one study intervention appendix is open at the time of enrollment. If multiple study intervention appendices are open, a participant may be excluded from any study intervention appendix based on contraindications listed in the study intervention appendix, current use of study intervention, or known allergy/sensitivity/hypersensitivity yet remain eligible for the remaining study intervention appendices.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,074 participants in 2 patient groups

Hypersomnia Arm (Appendix A)

Other group

Description:

This is a double-blind, phase 2, randomized, placebo-controlled interventional trial of a wake-promoting drug (modafinil or solriamfetol) to treat hypersomnia, defined by elevated scores (\> 55) on the PROMIS 8a SRI scale, in participants with PASC. Participants will be randomized to study drug or control. Participants who meet the eligibility criteria for modafinil will receive either active modafinil or modafinil-matched control. If modafinil is contraindicated, participants will be assessed for solriamfetol. If participants are eligible for solriamfetol, they will receive either active solriamfetol or 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. Anticipated enrollment is 474 participants. Details about the Hypersomnia Appendix are available under NCT06404099.

Treatment:

Drug: Solriamfetol

Drug: Modafinil

Drug: Modafinil Placebo

Drug: Solriamfetol Placebo

Complex PASC related Sleep Disturbances (CPSD) Arm (Appendix B )

Other group

Description:

This is a double-blind, phase 2, randomized, placebo-controlled, interventional trial that combines brief education and a tailored sleep timing prescription for CPSD with therapies that modify circadian timing for participants who report poor sleep quality or daytime sleep-related impairment, defined by elevated scores (≥55) on the PROMIS 8b SD scale, in participants with symptoms that occurred or worsened after COVID-19 infection. Interventions involve tailored lighting (TL) and melatonin. Participants will be randomly assigned to 1 of 4 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 BBT-CPSD. It is a 2x2 factorial design schema. The intervention duration will be 8 weeks. Anticipated enrollment for this appendix is 600 participants. Additional details about the CPSD Appendix are available under NCT06404112.

Treatment:

Drug: Melatonin

Drug: Melantonin Placebo

Device: Tailored lighting (TL) Placebo

Device: Tailored lighting (TL) Active