RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms

Sponsor

Duke University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05965752

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.

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.

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 active comparator will be considered part of pooled analyses if the intervention was active at the time of the participant's 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 active comparator 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 active comparator 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 Goal-oriented attentional self-regulation (GOALS) 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:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

≥ 18 years of age at the time of enrollment
PROMIS-Cog T-score < 40
Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization

Suspected case of SARS-CoV-2 infection - three options, A through C:

A. Met clinical OR epidemiological criteria:

Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia; b. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster;

Presented acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough, with onset within the last 10 days, and who requires hospitalization; or
Presented with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

Probable case of SARS-CoV-2 infection, defined as having met clinical criteria above AND was a contact of a probable or confirmed case or was linked to a COVID-19 cluster.

Confirmed case of SARS-CoV-2 infection - two options, A through B:

Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
Met clinical AND/OR epidemiological criteria (See suspected case A.a.), with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

Suspected and probable cases will only be allowed if they occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.

Cognitive dysfunction symptoms following a SARS-CoV-2 infection that have persisted for at least 12 weeks and are still present at the time of consent
Fluent in English or Spanish language
Willing and able to provide informed consent, complete the intervention, complete the intervention assessments, and return for all of the necessary follow-up visits

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

Prior or active unstable or progressive major psychiatric or neurologic condition that would not show improvement and could hide treatment effect and is not related to SARS-CoV-2 infection, at the investigator's discretion, including, but not limited to, the following examples:

Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc.
Past traumatic brain injury occurrence still associated with active post-concussive symptoms c. Uncontrolled seizure disorder, such as having at least one seizure in the last year that is adjudicated by clinical judgement d. Post-stroke deficits that may interfere with assessment, such as language or communication difficulties, aphasia, etc.
Formal thought disorders, such as schizophrenia, etc. f. Any neuropsychiatric or neurologic disorder uncontrolled for the previous six months or that may interfere with assessment, at discretion of the investigator

Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection
Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
Current use of symptomatic therapies including prescribed or illicit stimulants, amantadine, N-methyl-D-aspartate receptor antagonists (e.g., memantine, dissociative drugs)
Current use of a stimulant for treating any PASC-related symptom
Current diagnosis of alcohol and substance use disorders

Prior use disorders acceptable if abstinence achieved and maintained for at least 12 months before study enrollment

Insufficient visual, auditory, and motor function to participate in intervention and assessments
Known pregnancy
Current or recent use (within the last 2 months) of intervention*
Known allergy/sensitivity/hypersensitivity to components of the intervention or comparator*
Currently receiving/using intervention from another clinical trial, such as another RECOVER trial
Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
The site investigator has the discretion to determine whether a participant is too cognitively impaired to participate and should instead be referred for clinical evaluation.

Exclusions specific to intervention appendices are listed in each appendix.

Relevant if only one intervention appendix is open at the time of enrollment, though exclusion may be qualified in the appendix. If multiple intervention appendices are open, a participant may be excluded from any intervention appendix based on contraindications listed in the intervention appendix, current use of intervention, or known allergy/sensitivity/hypersensitivity and still remain eligible for the remaining intervention appendices.

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