The platform protocol is designed to be flexible so that it is suitable for a range ofstudy settings and intervention types. Therefore, the platform protocol provides ageneral protocol structure that can be shared by multiple interventions and allowscomparative analysis across the interventions. For example, objectives, measures, andendpoints are generalized in the platform protocol, but intervention-specific featuresare detailed in separate appendices.This platform protocol is a prospective, multi-center, multi-arm, randomized controlledplatform trial evaluating potential interventions for PASC-mediated sleep disturbances.The hypothesis is that symptoms of sleep and circadian disorders that emerge in patientswith PASC can be improved by phenotype-targeted interventions. Specific sleep andcircadian disorders addressed in this protocol include sleep-related daytime impairment(referred to as hypersomnia) and complex PASC-related sleep disturbance (reflectingsymptoms of insomnia and sleep-wake rhythm disturbance).
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.
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.
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.
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.
Banner University Medical Center Phoenix
Phoenix, Arizona, United States
University of Arizona Banner Medical Center
Tucson, Arizona, United States
University of California San Francisco General Hospital
San Francisco, California, United States
Stanford University
Stanford, California, United States
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Denver Health and Hospital Authority
Denver, Colorado, United States
Howard University Hospital
Washington, District of Columbia, United States
University of Florida College of Medicine Jacksonville
Jacksonville, Florida, United States
Atlanta VA Medical Center
Atlanta, Georgia, United States
Grady Memorial Hospital
Atlanta, Georgia, United States
Morehouse School of Medicine
Atlanta, Georgia, United States
Emory University
Atlanta, Georgia, United States
Emory Hope Clinic
Decatur, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Cook County Health Specialty Care Center
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Illinois at Chicago
Chicago, Illinois, United States
NorthShore Medical Group
Evanston, Illinois, United States
Saint Francis Medical Center
Peoria, Illinois, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
University of Kentucky
Lexington, Kentucky, United States
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States
Jadestone Clinical Research, LLC
Silver Spring, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Womens Hospital
Boston, Massachusetts, United States
Boston Medical Center
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr.
Boston, Massachusetts, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Rutgers University - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States
University of New Mexico
Albuquerque, New Mexico, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
East Carolina University
Greenville, North Carolina, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
University Hospitals of Cleveland Medical Center
Cleveland, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Southwest Family Medicine Associates
Dallas, Texas, United States
Houston Methodist Hospital
Houston, Texas, United States
University of Texas Health Science Center at Houston
Houston, Texas, United States
New Dawn Wellness and Medical Research Center
Houston, Texas, United States
University of Virginia Health System
Charlottesville, Virginia, United States
University Physicians and Surgeons (DBA Marshall Health)
Huntington, West Virginia, United States
West Virginia Clinical and Translational Science Institute
Morgantown, West Virginia, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Jaelyn R Linski, BA, CCRC
919-668-8060
recoverresearch@duke.edu
Barrie L Harper, BSMT (ASCP) PMP
recoverresearch@duke.edu