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

Long COVID Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05965752
• Other study ID #: Pro00112477
• Secondary ID: OTA-21-015G
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: December 2024

Study information

• Verified date: October 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 315
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

following criteria:

1. = 18 years of age at the time of enrollment

2. PROMIS-Cog T-score < 40

3. 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: a. 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; B. 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 C. 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: A. Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. 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.

4. 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

5. Fluent in English or Spanish language

6. 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:

1. 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: a. Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc. b. 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. e. 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

2. Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection

3. Known active acute SARS-CoV-2 infection = 4 weeks from consent

4. Current use of symptomatic therapies including prescribed or illicit stimulants, amantadine, N-methyl-D-aspartate receptor antagonists (e.g., memantine, dissociative drugs)

5. Current use of a stimulant for treating any PASC-related symptom

6. Current diagnosis of alcohol and substance use disorders a. Prior use disorders acceptable if abstinence achieved and maintained for at least 12 months before study enrollment

7. Insufficient visual, auditory, and motor function to participate in intervention and assessments

8. Known pregnancy

9. Current or recent use (within the last 2 months) of intervention*

10. Known allergy/sensitivity/hypersensitivity to components of the intervention or comparator*

11. Currently receiving/using intervention from another clinical trial, such as another RECOVER trial

12. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study

1. 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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• COVID-19
• Long COVID
• Long Covid-19

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Beth Israel Daeconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	NYU Langone Health/Brooklyn Hospital	Brooklyn	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Florida College of Medicine Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	West Virginia Clinical and Translational Science Institute	Morgantown	West Virginia
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Banner University Medical Center Phoenix	Phoenix	Arizona
United States	University of Utah Hospitals and Clinics	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	Jadestone Clinical Research	Silver Spring	Maryland
United States	North Shore University Health System/Evanston Hospital	Skokie	Illinois
United States	Stanford University	Stanford	California
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Banner University Medical Center- Tucson	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Change on an objective neurocognitive battery scores		Baseline, EOI (Day 70), EOS (Day 160)
Secondary	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)
Secondary	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)

External Links

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