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Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
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.
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Double blind

Arm Groups

ArmDescriptionAssigned Intervention
Other
Hypersomnia Arm (Appendix A) 		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 (> 60) 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.
  • 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.
  • Drug: 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.
  • Drug: 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.
  • Drug: 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.
Other
Complex PASC related Sleep Disturbances (CPSD) Arm (Appendix B ) 		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 (≥60) 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.
  • Drug: 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.
  • Drug: 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.
  • Device: 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.

Recruiting Locations

Banner University Medical Center Phoenix
Phoenix, Arizona 85006
Contact:
Joyce Lee-Iannotti, MD

More Details

Status
Recruiting
Sponsor
Duke University

Study Contact

Jaelyn R Linski, BA, CCRC
919-668-8060
recoverresearch@duke.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.