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

Sponsor

Duke University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05965739

Collaborator

(none)

315

Enrollment

Locations

Arms

Anticipated Duration (Months)

157.5

Patients Per Site

9.8

Patients Per Site Per Month

Study Details

Study Description

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-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..

Condition or Disease	Intervention/Treatment	Phase
Long COVID Long Covid19 Long Covid-19	Other: BrainHQ/Active Comparator Activity Other: BrainHQ Other: PASC CoRE Device: tDCS-active Device: tDCS-sham	N/A

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:

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

315 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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 (Participant, Care Provider, 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.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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.
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.
Characterize the intervention's safety as measured by the proportion of Serious Adverse Events [Baseline to EOS (Day 160)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Health Science Center at Houston	Houston	Texas	United States	77030
2	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229

Sponsors and Collaborators

Duke University

Investigators

Study Chair: Kanecia Zimmerman, MD PhD, Duke University
Study Chair: Daniel Laskowitz, MD MHS, Duke University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Related Info

Publications

None provided.

Responsible Party:

Duke University

ClinicalTrials.gov Identifier:

NCT05965739

Other Study ID Numbers:

Pro00112477_A
OTA-21-015G

First Posted:

Jul 28, 2023

Last Update Posted:

Aug 3, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Duke University

PASC

Cognitive

Additional relevant MeSH terms:

COVID-19

Post-Acute COVID-19 Syndrome

Study Results

No Results Posted as of Aug 3, 2023