RECOVER-SLEEP: Platform Protocol

Sleep Disturbance 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: NCT06404086
• Other study ID #: Pro00112484
• Secondary ID: OTA-21-015G
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: July 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: 1074
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 = 60**

** 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.

Related Conditions & MeSH terms

• Disorders of Excessive Somnolence
• Dyssomnias
• Hypersomnia
• Long COVID
• Long COVID-19
• Parasomnias
• Sleep Disturbance

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

Device:
• Tailored lighting (TL) Active
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.
• Tailored lighting (TL) Placebo
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total number of participants enrolled in each Appendix	Total number of participants enrolled in each Appendix will be reported. Appendix-specific outcome measure data will be reported under the associated NCT#.	12 months

External Links

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