RECOVER-NEURO: Platform Protocol, Appendix_A to Measure the Effects of BrainHQ, PASC CoRE and tDCS Interventions on Long COVID Symptoms

NCT ID: NCT05965739

Last Updated: 2025-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

328 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-01

Study Completion Date

2024-12-17

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

This design seeks to evaluate each intervention relative to the Active Comparator. The BrainHQ (alone) arm is important because the intervention is commercially available, accessible, relatively inexpensive, and does not require trained personnel to administer. BrainHQ has been also been proven effective in other studies of cognitive dysfunction such as studies in aging, mild cognitive impairment, traumatic brain injury, among others. The BrainHQ + PASC CoRE arm and the BrainHQ + tDCS arms are suspected to provide cognitive improvements beyond BrainHQ alone through different mechanisms. Both PASC CoRE and tDCS have extensive prior use and have demonstrated utility in improving aspects of cognitive function in other clinical settings..

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Participants will be randomized equally across the five arms:

1. Active Comparator (video games)
2. BrainHQ
3. BrainHQ + PASC CoRE
4. BrainHQ + tDCS-active
5. BrainHQ + tDCS-sham

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Long COVID Long Covid19 Long Covid-19

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Participants assigned to control will be considered part of pooled analyses if the intervention was active at the time of their 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 control 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 control inside the specific intervention appendix the participants were randomized to at the first stage of the randomization procedure.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

BrainHQ Active Comparator

5 sessions/week at 30 min/session

Group Type ACTIVE_COMPARATOR

BrainHQ/Active Comparator Activity

Intervention Type 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

5 sessions/week at 30 min/session

Group Type EXPERIMENTAL

BrainHQ

Intervention Type 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.

BrainHQ + PASC CoRE

BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session

Group Type EXPERIMENTAL

BrainHQ

Intervention Type 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.

PASC CoRE

Intervention Type 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.

Brain HQ + tDCS-active

2.0 mA stimulation delivered for 30 min during each BrainHQ session

Group Type EXPERIMENTAL

BrainHQ

Intervention Type 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.

tDCS-active

Intervention Type 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-sham

Inactive stimulation delivered for 30 min during each BrainHQ session

Group Type PLACEBO_COMPARATOR

BrainHQ

Intervention Type 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.

tDCS-sham

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type OTHER

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.

Intervention Type OTHER

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.

Intervention Type OTHER

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.

Intervention Type DEVICE

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.

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Exclusion Criteria

1. Presence of metal objects in the head or neck
2. Skin disorders or skin-sensitive areas near tDCS stimulation locations that would interfere with electrode placement or increase the risk of stimulation-induced damage, at the investigator's discretion
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Kanecia Zimmerman, MD PhD

Role: STUDY_CHAIR

Duke University

Daniel Laskowitz, MD MHS

Role: STUDY_CHAIR

Duke University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

All sites listed under NCT05965752

Durham, North Carolina, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Knopman DS, Laskowitz DT, Koltai DC, Charvet LE, Becker JH, Federman AD, Wisnivesky J, Mahncke H, Van Vleet TM, Bateman L, Kim DY, O'Steen A, James M, Silverstein A, Lokhnygina Y, Rich J, Feger BJ, Zimmerman KO. RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC). Trials. 2024 May 17;25(1):326. doi: 10.1186/s13063-024-08156-z.

Reference Type DERIVED
PMID: 38755688 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Informed Consent Form

View Document

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

OTA-21-015G

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

1OT2HL156812-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00112477_A

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Interdisciplinary Interventions After mTBI
NCT06815692 NOT_YET_RECRUITING