RECOVER-NEURO

Currently Recruiting: Participants

Study Drug/Intervention:

Appendix A is recruiting 315 across 5 arms with 63 participants randomized to the each of the following:

• Active Comparator
• BrainHQ (alone)
• BrainHQ + PASC-CoRE arm
• BrainHQ + tDCS sham arm
• BrainHQ + tDCS active arm

Study Timeline: This study is expected to conclude in December 2024.

ClinicalTrials.gov ID: NCT05965739

Objectives

Primary

Evaluate the intervention’s effect on cognitive function versus comparator

Secondary

• Assess the intervention’s effect on cognitive patient-reported outcomes (PROs) versus comparator
• Compare the intervention’s effect on an objective neurocognitive battery versus comparator
• Evaluate the intervention’s durable effect on cognitive function versus comparator
• Characterize the intervention’s safety

Exploratory

Assess the intervention’s effect on exploratory PROs versus comparator

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 Organization³⁴

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

1. Met clinical OR epidemiological criteria:
   1. 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;
   2. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster;
2. 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
3. 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:

1. Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
2. Met clinical AND/OR epidemiological criteria (See suspected case 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 , at the investigator’s discretion, including, but not limited to, the following examples:
   1. Progressive neurodegenerative disease, such as Alzheimer’s disease, Parkinson’s disease, etc.
   2. Past traumatic brain injury occurrence still associated with active post-concussive symptoms
   3. Uncontrolled seizure disorder, such as having at least one seizure in the last year that is adjudicated by clinical judgment
   4. Post-stroke deficits that may interfere with assessment, such as language or communication difficulties, aphasia, etc.
   5. Formal thought disorders, such as schizophrenia, etc. 
   6. 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. History of electroconvulsive therapy
5. Current use of any medication for treating PASC-related symptoms
6. Attention-deficit/hyperactivity disorder (ADHD) diagnosis following the onset of PASC**
7. Current diagnosis of alcohol and substance use disorders
   1. Prior use disorders acceptable if abstinence achieved and maintained for at least 12 months before study enrollment
8. Insufficient visual, auditory, and motor function to participate in intervention and assessments
9. Known pregnancy
10. Current or recent use (within the last 2 months) of the intervention***
11. Known allergy/sensitivity/hypersensitivity to components of the intervention or comparator***
12. Currently receiving/using intervention from another clinical trial, such as another RECOVER trial****
13. 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.

*Participants who are currently taking prohibited medications or alternative therapies may undergo a 30-day washout period, which will be determined by the site principal investigator based on standard of care practices. However, if the site principal investigator determines that the participants must continue taking their current medication regimens or alternative therapies, then the participants will be ineligible for enrollment.

**Participants diagnosed with ADHD prior to PASC-related symptoms and who are compliant on stable doses of medication may participate per the investigator’s discretion. Participants should agree to maintain a stable dose of their medication while in the trial.

*** 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.

****Following another interventional trial’s end-of-study visit, participants must wait 90 days before enrolling into NEURO.

Sponsor

DCRI

Funder

National Institutes of Health

• PI: Daniel Laskowitz, MD, MHS
• PL: Ashley O’Steen