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

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

Status

Completed

Phases

Unknown

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05965739

Enrollment

328

Registered

2023-07-28

Start date

2023-09-01

Completion date

2024-12-17

Last updated

2026-08-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Long COVID, Long Covid19, Long Covid-19

Keywords

PASC, Cognitive

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..

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. 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

Interventions

OTHERBrainHQ/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.

OTHERBrainHQ

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.

OTHERPASC 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.

DEVICEtDCS-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.

DEVICEtDCS-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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Masking description

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.

Intervention 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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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

Exclusion criteria

1\. See NCT05965752 for RECOVER-NEURO: Platform Protocol level

Design outcomes

Primary

Measure	Time frame	Description
Change in Everyday Cognition 2 (ECog2)	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

Measure	Time frame	Description
Change on Symbol Digit Modalities Test	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.
Change in Verbal Fluency	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.
Change in Total Time to Complete the Digit Vigilance Test	Baseline, End of Intervention - EOI (Day 70), End of Study (EOS) (Day 160)	—
Change on NIH Toolbox Flanker Inhibitory Control and Attention Test	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.
Change in CogState Detection Score	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.
Change in CogState Identification Score	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.
Change in CogState One Back Primary Score	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.
Change in Everyday Cognition 2 (ECog2)	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.
Total Number of Serious Adverse Events (SAEs) or Unanticipated Adverse Device Effects (UADEs)	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.
Change on Auditory Verbal Learning Test	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.
Change in PROMIS-cognitive Function - Short Form 8a (PROMIS-Cog) Total Score	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.

Countries

United States

Contacts

STUDY_CHAIRKanecia Zimmerman, MD PhD

Duke University

STUDY_CHAIRDaniel Laskowitz, MD MHS