This platform protocol is designed to be flexible so that it is suitable for a wide rangeof settings within health care systems, for remote settings, and in community settingswhere it can be integrated into COVID-19 programs and subsequent treatment plans.This protocol is a prospective, multi-center, multi-arm, randomized, controlled platformtrial evaluating potential interventions for PASC-mediated cognitive dysfunction. Thehypothesis is that PASC-associated dysfunction in cognitive domains, such as executivefunction and attention, may be improved by interventions that selectively focus onenhancing those domains.This design seeks to evaluate each intervention relative to the Active Comparator. TheBrainHQ (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 dysfunctionsuch as studies in aging, mild cognitive impairment, traumatic brain injury, amongothers. The BrainHQ + PASC CoRE arm and the BrainHQ + tDCS arms are suspected to providecognitive improvements beyond BrainHQ alone through different mechanisms. Both PASC CoREand tDCS have extensive prior use and have demonstrated utility in improving aspects ofcognitive function in other clinical settings..
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
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.
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 adapted from
Goal Management Training and other evidence based programs that improve attention and
executive functions, among other cognitive domains.
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.
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.
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:
1. Presence of metal objects in the head or neck
2. 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
All sites listed under NCT05965752
Durham 4464368, North Carolina 4482348, United States