RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms
NCT ID: NCT05965752
Last Updated: 2025-07-18
Study Results
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View full resultsBasic Information
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COMPLETED
NA
328 participants
INTERVENTIONAL
2023-09-01
2024-06-10
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
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.
TREATMENT
TRIPLE
Sites will be informed to which intervention appendix participants are randomized, but, when applicable, not whether the participants are allocated to the active intervention arm or active comparator arm within that appendix. The participants and investigators will be blinded throughout the study, when possible.
If open intervention appendices do not have the ability to pool controls but have independent controls, at the second stage participants will be randomized in a 1:1 ratio to intervention vs active comparator inside the specific intervention appendix the participants were randomized to at the first stage of the randomization procedure.
Study Groups
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BrainHQ Active Comparator
5 sessions/week at 30 min/session
BrainHQ/Active Comparator Activity
BrainHQ platform provides a set of cognitive activities, like puzzles and games, that are cognitively stimulating and actively engage participants but do not continuously and adaptively challenge them. These activities are designed to be a face-valid, active comparison approach to cognitive therapy, thus participants are blinded, attention time is matched, and overall user experience is identical to the active arms.
BrainHQ
5 sessions/week at 30 min/session
BrainHQ
BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.
BrainHQ + PASC CoRE
BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 30 min/session
BrainHQ
BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.
PASC CoRE
PASC CoRE is a manualized, adaptable cognitive rehabilitation intervention adapted from Goal Management Training and other evidence based programs that improve attention and executive functions, among other cognitive domains.
Brain HQ + tDCS-active
2.0 mA stimulation delivered for 30 min during each BrainHQ session
BrainHQ
BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.
tDCS-active
Transcranial direct current stimulation (tDCS) will use a device specifically for home-based use. This device delivers a weak electrical current of 2.0 mA passed through two electrodes placed on the scalp to target the dorsolateral prefrontal cortex region of the brain. The electrodes are single-use for each session and can be attached to a headset by snapping into place.
The device has a user-friendly interface and a large-button keypad, making it is easy to use at home.
Brain HQ + tDCS-sham
Inactive stimulation delivered for 30 min during each BrainHQ session
BrainHQ
BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.
tDCS-sham
tDCS devices used in the sham arm will be pre-programmed to deliver the same ramp up/down at the beginning/end of the 30-minute period as the active arm, except with no current otherwise delivered during the session.
Interventions
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BrainHQ/Active Comparator Activity
BrainHQ platform provides a set of cognitive activities, like puzzles and games, that are cognitively stimulating and actively engage participants but do not continuously and adaptively challenge them. These activities are designed to be a face-valid, active comparison approach to cognitive therapy, thus participants are blinded, attention time is matched, and overall user experience is identical to the active arms.
BrainHQ
BrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity.
PASC CoRE
PASC CoRE is a manualized, adaptable cognitive rehabilitation intervention adapted from Goal Management Training and other evidence based programs that improve attention and executive functions, among other cognitive domains.
tDCS-active
Transcranial direct current stimulation (tDCS) will use a device specifically for home-based use. This device delivers a weak electrical current of 2.0 mA passed through two electrodes placed on the scalp to target the dorsolateral prefrontal cortex region of the brain. The electrodes are single-use for each session and can be attached to a headset by snapping into place.
The device has a user-friendly interface and a large-button keypad, making it is easy to use at home.
tDCS-sham
tDCS devices used in the sham arm will be pre-programmed to deliver the same ramp up/down at the beginning/end of the 30-minute period as the active arm, except with no current otherwise delivered during the session.
Eligibility Criteria
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Inclusion 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
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.
18 Years
ALL
No
Sponsors
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Duke University
OTHER
Responsible Party
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Principal Investigators
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Kanecia Zimmerman, MD PhD
Role: STUDY_CHAIR
Duke University
Daniel Laskowitz, MD MHS
Role: STUDY_CHAIR
Duke University
Locations
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Banner University Medical Center Phoenix
Phoenix, Arizona, United States
Banner University Medical Center- Tucson
Tucson, Arizona, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
Stanford University
Stanford, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, United States
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
University of Florida College of Medicine Jacksonville
Jacksonville, Florida, United States
Rush University Medical Center
Chicago, Illinois, United States
OSF Healthcare
Peoria, Illinois, United States
North Shore University Health System/Evanston Hospital
Skokie, Illinois, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Jadestone Clinical Research
Silver Spring, Maryland, United States
Boston Medical Center
Boston, Massachusetts, United States
Beth Israel Daeconess Medical Center
Boston, Massachusetts, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
NYU Langone Health/Brooklyn Hospital
Brooklyn, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Case Western Reserve University
Cleveland, Ohio, United States
University of Texas Health Science Center at Houston
Houston, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
University of Utah Hospitals and Clinics
Salt Lake City, Utah, United States
University of Vermont
Burlington, Vermont, United States
University of Washington
Seattle, Washington, United States
West Virginia Clinical and Translational Science Institute
Morgantown, West Virginia, United States
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Document Type: Informed Consent Form
Related Links
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Related Info
Other Identifiers
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OTA-21-015G
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
Pro00112477
Identifier Type: -
Identifier Source: org_study_id
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