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

NCT05965739 | Completed DMC

• 3 other identifiers: Pro00112477_AOTA-21-015G1OT2HL156812-01
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

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. 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..

Conditions

Long COVID; Long Covid-19

Keywords

PASC; Cognitive

Outcome Measures

Primary Outcomes (1)

• Change in Everyday Cognition 2 (ECog2)

  Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.

  Baseline to End of Intervention (EOI) (Day 70)

Secondary Outcomes (4)

• Change in PROMIS-cognitive function - short form 8a (PROMIS-Cog) total score

  Baseline, EOI (Day 70), End of Study (EOS) (Day 160)

• Change on an objective neurocognitive battery scores

  Baseline, EOI (Day 70), EOS (Day 160)

• Change in Everyday Cognition 2 (ECog2)

  Baseline, EOS (Day 160)

• Characterize the intervention's safety as measured by the proportion of Serious Adverse Events, Unanticipated Adverse device Effects, and/or Events of Special Interest [Proportion of SAEs, UADEs, and/or ESIs.]

  Baseline to EOS (Day 160)

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 1 hr/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 not qualify if:

• Presence of metal objects in the head or neck
• 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

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

All sites listed under NCT05965752

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• Knopman DS, Koltai D, Laskowitz DT, Becker J, Charvet L, Wisnivesky J, Federman A, Silverstein A, Lokhnygina Y, Pilloni G, Haddad M, Mahncke H, Van Vleet T, Huang R, Cox W, Terry D, Karwowski J, McCray N, Lin JJ, McComsey GA, Singh U, Geng LN, Chu HY, Reece R, Moy J, Arvanitakis Z, Parthasarathy S, Patterson TF, Gupta A, Ostrosky-Zeichner L, Parsonnet J, Kiriakopoulos ET, Fong TG, Mullington J, Jolley S, Shah NS, Morimoto SS, Lee-Iannotti JK, Killgore WDS, Dwyer B, Stringer W, Isache C, Frontera JA, Krishnan JA, O'Steen A, James M, Harper BL, Zimmerman KO; RECOVER-NEURO Clinical Trial Group. Evaluation of Interventions for Cognitive Symptoms in Long COVID: A Randomized Clinical Trial. JAMA Neurol. 2026 Jan 1;83(1):49-59. doi: 10.1001/jamaneurol.2025.4415.

  PMID: 41212544 DERIVED

• 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.

  PMID: 38755688 DERIVED

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

Study Officials

• Kanecia Zimmerman, MD PhD

  Duke University

  STUDY CHAIR

• Daniel Laskowitz, MD MHS

  Duke University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• 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: September 19, 2024
• Study Completion: December 17, 2024
• Last Updated: May 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)