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

Not Applicable

Completed

Interventions: Other: BrainHQ/Active Comparator Activity
Other: BrainHQ
Device: tDCS-active
Other: PASC CoRE
Device: tDCS-sham

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Brain HQ + tDCS-active	tDCS-active	2.0 mA stimulation delivered for 30 min during each BrainHQ session
BrainHQ + PASC CoRE	PASC CoRE	BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session
BrainHQ Active Comparator	BrainHQ/Active Comparator Activity	5 sessions/week at 30 min/session
Brain HQ + tDCS-active	BrainHQ	2.0 mA stimulation delivered for 30 min during each BrainHQ session
BrainHQ	BrainHQ	5 sessions/week at 30 min/session
BrainHQ + PASC CoRE	BrainHQ	BrainHQ plus 9 group sessions at 1.5 hr/session and 3 individual sessions at 1 hr/session
Brain HQ + tDCS-sham	BrainHQ	Inactive stimulation delivered for 30 min during each BrainHQ session
Brain HQ + tDCS-sham	tDCS-sham	Inactive stimulation delivered for 30 min during each BrainHQ session

Primary Outcome Measures

Name	Time	Method
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 simple reaction time; respond when X happens and Choice reaction time; respond only if X happens.

Secondary Outcome Measures

Name	Time	Method
Change on an objective neurocognitive battery scores	Baseline, EOI (Day 70), EOS (Day 160)
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.
Change in PROMIS-cognitive function - short form 8a (PROMIS-Cog) total score	Baseline, 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.
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)