Long COVIDNCT05965752
RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms
A study testing BrainHQ/Active Comparator Activity, BrainHQ and PASC CoRE in people with Long COVID and Long COVID-19, run by Duke University at 24 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Long COVID, Long COVID-19, Long COVID19
- What is being tested?
- BrainHQ/Active Comparator Activity, BrainHQ and PASC CoRE
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 328 participants
- Where
- 24 sitesUnited States
- Study dates
- 1 Sep 2023to 10 Jun 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Met clinical OR epidemiological criteria:
Show all 17Show fewer
- 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;
- 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
- 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:
- Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
- 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
- Fluent in English or Spanish language
- Willing and able to provide informed consent, complete the intervention, complete the intervention assessments, and return for all of the necessary follow-up visits
Who cannot join
- 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:
- Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc.
- 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.
- 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
Show all 20Show fewer
- 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
- 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*
- Currently receiving/using intervention from another clinical trial, such as another RECOVER trial
- Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
- 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.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Boston Medical Center
Boston, Massachusetts, 02118
Beth Israel Daeconess Medical Center
Boston, Massachusetts, 02215
NYU Langone Health/Brooklyn Hospital
Brooklyn, New York, 11220
University of Vermont
Burlington, Vermont, 05401
Rush University Medical Center
Chicago, Illinois, 60612
Case Western Reserve University
Cleveland, Ohio, 44106
University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Florida College of Medicine Jacksonville
Jacksonville, Florida, 32256
University of Kansas Medical Center
Kansas City, Kansas, 66160
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
West Virginia Clinical and Translational Science Institute
Morgantown, West Virginia, 26506
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
OSF Healthcare
Peoria, Illinois, 61801
Banner University Medical Center Phoenix
Phoenix, Arizona, 85006
University of Utah Hospitals and Clinics
Salt Lake City, Utah, 84132
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
University of Washington
Seattle, Washington, 98109
Jadestone Clinical Research
Silver Spring, Maryland, 20904
North Shore University Health System/Evanston Hospital
Skokie, Illinois, 60076
Stanford University
Stanford, California, 94305
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90509
Banner University Medical Center- Tucson
Tucson, Arizona, 85719
About this study
Official title: RECOVER-NEURO: A Platform Protocol for Evaluation of Interventions for Cognitive Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
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.
Read the 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.
- Conditions
- Long COVID, Long COVID-19, Long COVID19
- Being tested
- BrainHQ/Active Comparator Activity, BrainHQ, PASC CoRE, tDCS-active, tDCS-sham
- Keywords
- PASC, Cognitive
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrainHQ/Active Comparator ActivityOther
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.
BrainHQOther
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 CoREOther
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-activeDevice
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-shamDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| BrainHQ Active Comparator | Active comparator | 5 sessions/week at 30 min/session Receives: Other: BrainHQ/Active Comparator Activity |
| BrainHQ | Experimental | 5 sessions/week at 30 min/session Receives: Other: BrainHQ |
| BrainHQ + PASC CoRE | Experimental | BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 30 min/session Receives: Other: BrainHQ; Other: PASC CoRE |
| Brain HQ + tDCS-active | Experimental | 2.0 mA stimulation delivered for 30 min during each BrainHQ session Receives: Other: BrainHQ; Device: tDCS-active |
| Brain HQ + tDCS-sham | Placebo comparator | Inactive stimulation delivered for 30 min during each BrainHQ session Receives: Other: BrainHQ; Device: tDCS-sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Participants Enrolled in Each Appendix
Appendix-specific outcome measure data will be reported under the associated NCT ID.
Measured: 160 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2023
- Study start1 Sep 2023
- Primary completion10 Jun 2024
- Study completion10 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Long COVIDStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 328 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kanecia Zimmerman, MD PhD, Study chair, Duke UniversityDaniel Laskowitz, MD MHS, Study chair, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05965752
- Sponsor's protocol ID
- Pro00112477
- Other IDs
- OTA-21-015G
- Status last verified
- Jul 2025
- First submitted
- 25 Jul 2023
- Last updated
- 18 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: The investigators will share the summary of results on the study website: https://recovercovid.org/
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RECOVER-NEURO: A Platform Protocol for Evaluation of Interventions for Cognitive Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
- ClinicalTrials.gov ID
- NCT05965752
- Acronym / sponsor ID
- Pro00112477
- Conditions
- Long COVID, Long COVID-19, Long COVID19
- Keywords
- PASC, Cognitive
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 328 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 10 Jun 2024 (actual)
- Study completion
- 10 Jun 2024 (actual)
- First posted
- 28 Jul 2023 (actual)
- Results
- Posted 18 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
- 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.
| Arm | Type | Receives |
|---|---|---|
| BrainHQ Active Comparator | Active comparator | Other: BrainHQ/Active Comparator Activity5 sessions/week at 30 min/session |
| BrainHQ | Experimental | Other: BrainHQ5 sessions/week at 30 min/session |
| BrainHQ + PASC CoRE | Experimental | Other: BrainHQ, Other: PASC CoREBrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 30 min/session |
| Brain HQ + tDCS-active | Experimental | Other: BrainHQ, Device: tDCS-active2.0 mA stimulation delivered for 30 min during each BrainHQ session |
| Brain HQ + tDCS-sham | Placebo comparator | Other: BrainHQ, Device: tDCS-shamInactive stimulation delivered for 30 min during each BrainHQ session |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
- 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.
Key exclusion criteria (20 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrainHQ/Active Comparator ActivityBrainHQ 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. | Other | BrainHQ Active Comparator |
| BrainHQBrainHQ is an online cognitive training program, and has been used to improve cognitive function among persons with cognitive impairment based on principles of neuroplasticity. | Other | Brain HQ + tDCS-active, Brain HQ + tDCS-sham, BrainHQ, BrainHQ + PASC CoRE |
| PASC CoREPASC 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. | Other | BrainHQ + PASC CoRE |
| tDCS-activeTranscranial 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. | Device | Brain HQ + tDCS-active |
| tDCS-shamtDCS 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. | Device | Brain HQ + tDCS-sham |
Primary outcome
Total Number of Participants Enrolled in Each Appendix
Time frame: 160 Days
Appendix-specific outcome measure data will be reported under the associated NCT ID.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. The investigators will share the summary of results on the study website: https://recovercovid.org/
Related trials for Long COVID
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Not yet recruitingPhase 3
The Study of Brave-LC LDN Treatment Trial
Post-acute COVID-19 Syndrome
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Enrolling by invitationPhase 2
Immunotherapy for Neurological Post-Acute Sequelae of SARS-CoV-2
Systemic Inflammation, Neuroinflammation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kanecia Zimmerman, MD PhD study chair
Duke University
Daniel Laskowitz, MD MHS study chair
Duke University
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing BrainHQ/Active Comparator Activity, BrainHQ and PASC CoRE in people with Long COVID and Long COVID-19, run by Duke University at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Number of Participants Enrolled in Each Appendix (time frame: 160 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2025.