Clinical trial NCT05965752: RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms
Official title: RECOVER-NEURO: A Platform Protocol for Evaluation of Interventions for Cognitive Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Long COVID
Long Covid19
Long Covid-19
Keywords: PASC
Cognitive
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2023-07-28
Enrollment: 328
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: To achieve blinding and an equitable randomization probability, a two-step randomization process will be used. The study will employ a simple (unstratified) randomization scheme.

At the first stage, each participant will be assigned with equal probability to one of the intervention appendices for which the participant is eligible, after applying any intervention-specific safety exclusions. At the second stage, each participant will be assigned according to the specific appendix's randomization procedure. Participants will have an equal chance of being randomized into any of the intervention groups.
Primary purpose: TREATMENT

Brief summary: This platform protocol is designed to be flexible so that it is suitable for a wide range of settings within health care systems, for remote settings, and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans.

This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating potential interventions for PASC-mediated cognitive dysfunction. The hypothesis is that PASC associated dysfunction in cognitive domains, such as executive function and attention, may be improved by interventions that selectively focus on enhancing those domains.

Detailed description: Participants will be randomized to one of the intervention appendices that are actively enrolling at the time of randomization. Intervention appendices may be added or removed according to adaptive design and/or emerging evidence. Various interventions will be studied.

Eligibility criteria: 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. PROMIS-Cog T-score \< 40
3. 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 clinical OR epidemiological criteria:

   a. 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; b. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster;

   B. Presented acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough, with onset within the last 10 days, and who requires 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 clinical criteria above AND was a contact of a probable or confirmed case or was linked to a COVID-19 cluster.

   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 AND/OR epidemiological criteria (See suspected case A.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.
4. Cognitive dysfunction symptoms following a SARS-CoV-2 infection that have persisted for at least 12 weeks and are still present at the time of consent
5. Fluent in English or Spanish language
6. Willing and able to provide informed consent, complete the intervention, complete the intervention assessments, and return for all of the necessary follow-up visits

Exclusion Criteria:

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

1. Prior or active unstable or progressive major psychiatric or neurologic condition that would not show improvement and could hide treatment effect and is not related to SARS-CoV-2 infection, at the investigator's discretion, including, but not limited to, the following examples:

   a. Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc.

   b. Past traumatic brain injury occurrence still associated with active post-concussive symptoms c. Uncontrolled seizure disorder, such as having at least one seizure in the last year that is adjudicated by clinical judgement d. Post-stroke deficits that may interfere with assessment, such as language or communication difficulties, aphasia, etc.

   e. Formal thought disorders, such as schizophrenia, etc. f. Any neuropsychiatric or neurologic disorder uncontrolled for the previous six months or that may interfere with assessment, at discretion of the investigator
2. Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection
3. Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
4. Current use of symptomatic therapies including prescribed or illicit stimulants, amantadine, N-methyl-D-aspartate receptor antagonists (e.g., memantine, dissociative drugs)
5. Current use of a stimulant for treating any PASC-related symptom
6. Current diagnosis of alcohol and substance use disorders

   a. Prior use disorders acceptable if abstinence achieved and maintained for at least 12 months before study enrollment
7. Insufficient visual, auditory, and motor function to participate in intervention and assessments
8. Known pregnancy
9. Current or recent use (within the last 2 months) of intervention\*
10. Known allergy/sensitivity/hypersensitivity to components of the intervention or comparator\*
11. Currently receiving/using intervention from another clinical trial, such as another RECOVER trial
12. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study

    1. The site investigator has the discretion to determine whether a participant is too cognitively impaired to participate and should instead be referred for clinical evaluation.

Exclusions specific to intervention appendices are listed in each appendix.

\* Relevant if only one intervention appendix is open at the time of enrollment, though exclusion may be qualified in the appendix. If multiple intervention appendices are open, a participant may be excluded from any intervention appendix based on contraindications listed in the intervention appendix, current use of intervention, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining intervention appendices.

Primary outcomes:
measure: Total number of participants enrolled in each Appendix
timeFrame: 160 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center Phoenix
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center- Tucson
state: Arizona
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida College of Medicine Jacksonville
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Peoria
country: United States
facility: OSF Healthcare
state: Illinois
city: Skokie
country: United States
facility: North Shore University Health System/Evanston Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Silver Spring
country: United States
facility: Jadestone Clinical Research
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Daeconess Medical Center
state: Massachusetts
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Brooklyn
country: United States
facility: NYU Langone Health/Brooklyn Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia Clinical and Translational Science Institute
state: West Virginia
Study officials:
affiliation: Duke University
name: Kanecia Zimmerman, MD PhD
role: STUDY_CHAIR
affiliation: Duke University
name: Daniel Laskowitz, MD MHS
role: STUDY_CHAIR
References: