RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms

NCT05965752 | Completed Results DMC FDA Device

• 2 other identifiers: Pro00112477OTA-21-015G
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 24

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.

Conditions

Long COVID; Long COVID19

Keywords

PASC; Cognitive

Outcome Measures

Primary Outcomes (1)

• Total Number of Participants Enrolled in Each Appendix

  Appendix-specific outcome measure data will be reported under the associated NCT ID.

  160 Days

Study Arms (5)

BrainHQ Active Comparator

ACTIVE COMPARATOR

5 sessions/week at 30 min/session

Other: BrainHQ/Active Comparator Activity

BrainHQ

EXPERIMENTAL

5 sessions/week at 30 min/session

Other: BrainHQ

BrainHQ + PASC CoRE

EXPERIMENTAL

BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 30 min/session

Other: BrainHQ; Other: PASC CoRE

Brain HQ + tDCS-active

EXPERIMENTAL

2.0 mA stimulation delivered for 30 min during each BrainHQ session

Other: BrainHQ; Device: tDCS-active

Brain HQ + tDCS-sham

PLACEBO COMPARATOR

Inactive stimulation delivered for 30 min during each BrainHQ session

Other: BrainHQ; Device: tDCS-sham

Interventions

BrainHQ/Active Comparator Activity OTHER

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 Active Comparator

BrainHQ OTHER

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.

Brain HQ + tDCS-active; Brain HQ + tDCS-sham; BrainHQ; BrainHQ + PASC CoRE

PASC CoRE OTHER

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.

BrainHQ + PASC CoRE

tDCS-active DEVICE

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-active

tDCS-sham DEVICE

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.

Brain HQ + tDCS-sham

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• ≥ 18 years of age at the time of enrollment
• PROMIS-Cog T-score \< 40
• 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.
• 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

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• 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
• Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection
• Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
• Current use of symptomatic therapies including prescribed or illicit stimulants, amantadine, N-methyl-D-aspartate receptor antagonists (e.g., memantine, dissociative drugs)
• Current use of a stimulant for treating any PASC-related symptom
• 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
• Insufficient visual, auditory, and motor function to participate in intervention and assessments
• Known pregnancy
• Current or recent use (within the last 2 months) of intervention\*
• Known allergy/sensitivity/hypersensitivity to components of the intervention or comparator\*

Sponsors & Collaborators

• Duke University: lead

Study Sites (24)

Banner University Medical Center Phoenix

Phoenix, Arizona, 85006, United States

Location

Banner University Medical Center- Tucson

Tucson, Arizona, 85719, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90509, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Florida College of Medicine Jacksonville

Jacksonville, Florida, 32256, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

OSF Healthcare

Peoria, Illinois, 61801, United States

Location

North Shore University Health System/Evanston Hospital

Skokie, Illinois, 60076, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Jadestone Clinical Research

Silver Spring, Maryland, 20904, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Daeconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

NYU Langone Health/Brooklyn Hospital

Brooklyn, New York, 11220, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah Hospitals and Clinics

Salt Lake City, Utah, 84132, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

West Virginia Clinical and Translational Science Institute

Morgantown, West Virginia, 26506, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Daniel Laskowitz, MD
• Organization: Duke University

daniel.laskowitz@duke.edu

919-684-0056

Study Officials

• Kanecia Zimmerman, MD PhD

  Duke University

  STUDY CHAIR

• Daniel Laskowitz, MD MHS

  Duke University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants assigned to active comparator will be considered part of pooled analyses if the intervention was active at the time of the participant's enrollment and the participants were eligible to receive that intervention. This will result in approximately a 1:1 allocation ratio for any intervention to pooled control. 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 25, 2023
• First Posted: July 28, 2023
• Study Start: September 1, 2023
• Primary Completion: June 10, 2024
• Study Completion: June 10, 2024
• Last Updated: July 18, 2025
• Results First Posted: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)