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

Study Overview
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Brief Summary
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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-mediated declines 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
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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

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

Conditions
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Long COVID, Long Covid19, Long Covid-19

Intervention / Treatment
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* Other: BrainHQ/Active Comparator Activity
* Other: BrainHQ
* Other: PASC CoRE
* Device: tDCS-active
* Device: tDCS-sham


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BrainHQ Active Comparator<br>5 sessions/week at 30 min/session | Other: BrainHQ/Active Comparator Activity<br>* 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.<br>|
| Experimental: BrainHQ<br>5 sessions/week at 30 min/session | Other: BrainHQ<br>* 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.<br>|
| Experimental: BrainHQ + PASC CoRE<br>BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session | Other: BrainHQ<br>* 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.<br>Other: PASC CoRE<br>* PASC CoRE is a manualized, adaptable cognitive rehabilitation intervention with demonstrated efficacy in improving attention and executive functions, among other cognitive domains.<br>|
| Experimental: Brain HQ + tDCS-active<br>2.0 mA stimulation delivered for 30 min during each BrainHQ session | Other: BrainHQ<br>* 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.<br>Device: tDCS-active<br>* 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.<br>|
| Placebo Comparator: Brain HQ + tDCS-sham<br>Inactive stimulation delivered for 30 min during each BrainHQ session | Other: BrainHQ<br>* 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.<br>Device: tDCS-sham<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PROMIS-cognitive function - short form 8a (PROMIS-Cog) total score | 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. | 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) | 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, EOS (Day 160) | 
| Characterize the intervention's safety as measured by the proportion of Serious Adverse Events |  | Baseline to EOS (Day 160) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PASC, Cognitive