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Completed

NCT Number: NCT05965739

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

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..

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Key information

Conditions

Long COVID COVID-19 Chronic Disease Coronaviridae Infections Coronavirus Infections Disease Attributes Infections Long COVID-19 Long Covid19 Lung Diseases Nidovirales Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Pneumonia Pneumonia, Viral Post-Acute COVID-19 Syndrome Post-Infectious Disorders RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

All sites listed under NCT05965752

Durham, North Carolina, 27710, United States

About this study

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:

  • Active Comparator (video games)
  • BrainHQ
  • BrainHQ + PASC CoRE
  • BrainHQ + tDCS-active
  • BrainHQ + tDCS-sham

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • See NCT05965752 for RECOVER-NEURO: Platform Protocol level inclusion criteria which applies to this appendix

Exclusion criteria

  • See NCT05965752 for RECOVER-NEURO: Platform Protocol level exclusion criteria which applies to this appendix

Additional Appendix (Sub-study) Level Exclusion Criteria:

  • 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

Treatment and study plan

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

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

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.

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.

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.

Primary outcomes

  1. Change in Everyday Cognition 2 (ECog2)

    Time frame: Baseline to End of Intervention (EOI) (Day 70)

    Everyday Cognition 2 (ECog2) is a self-report, 41-item questionnaire used to measure the participant's perceived capacity to perform activities related to cognitive function, which could impact major activities of daily living and independence. Score ranges from 1 to 5, with 5 being worst.

Secondary outcomes

  1. Change in PROMIS-cognitive Function - Short Form 8a (PROMIS-Cog) Total Score

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    The PROMIS-Cog is the PROMIS short form for the cognitive function domain and is a self-report, 8-item questionnaire targeting cognitive function in the past seven days. Scores range from 22.4 to 63.5. Higher scores are better.

  2. Change on Auditory Verbal Learning Test

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    Trials #1-#5 report the total number correct across 5 trials. Trials #1-5 generate one total score, the individual scores for each trial are not analyzed. The Score for Trials #1-#5 range from 0-75; higher scores are better.

    Trial #8 reports the total number correct. Scores range from 0-15; higher scores are better.

    Trial #9 reports the total number correct recognition hits minus false positive. Scores range from 0-15; higher scores are better.

  3. Change on Symbol Digit Modalities Test

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    The Symbol Digit Modalities Test reports the total number correct on the test. Scores range from 0-110. Higher scores are better.

  4. Change in Verbal Fluency

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    The Verbal Fluency Semantic reports the total number correct. Scores range from 0-110. Higher scores are better.

  5. Change in Total Time to Complete the Digit Vigilance Test

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

  6. Change on NIH Toolbox Flanker Inhibitory Control and Attention Test

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    The Flanker Inhibitory Control and Attention Test Computed Score ranges from 0-10. Higher scores are better.

  7. Change in CogState Detection Score

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    CogState Detection Score is the mean of log10 transformed reaction times. Lower values are better.

  8. Change in CogState Identification Score

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    CogState Identification Score is the mean of log10 transformed reaction times for correct responses. Lower values are better.

  9. Change in CogState One Back Primary Score

    Time frame: Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)

    CogState One Back Primary Score is the arcsine transformation of the square root of the proportion of correct responses. The scale ranges from 0 to π/2. Higher scores are better.

  10. Change in Everyday Cognition 2 (ECog2)

    Time frame: Baseline, EOS (Day 160)

    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.

  11. Total Number of Serious Adverse Events (SAEs) or Unanticipated Adverse Device Effects (UADEs)

    Time frame: Baseline to EOS (Day 160)

    An SAE or serious suspected adverse reaction (SAR) or serious adverse reaction an AE that results in any of the following serious outcomes: Death, life-threatening, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, inpatient hospitalization or prolongation of existing hospitalization, congenital abnormality or birth defect, important medical event that may not result in one of the above outcomes, but may jeopardize the health of the study participant or require medical or surgical intervention to prevent one of the above outcomes from occurring. A UADE is any serious adverse effect, problem, or death caused by or associated with a device if that effect was not previously identified in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

RECOVER-NEURO: A Platform Protocol for Evaluation of Interventions for Cognitive Dysfunction in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Jul 28, 2023
Registry last updated
Aug 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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