RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC)

Trials. 2024 May 17;25(1):326. doi: 10.1186/s13063-024-08156-z.

Abstract

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work.

Methods: RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English.

Discussion: This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction.

Trial registration: ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

Keywords: Cognitive dysfunction; Cognitive rehabilitation; Cognitive training; Long-COVID; Post-acute sequelae of SARS-CoV-2 infection; Transcranial direct current stimulation; tDCS.

Publication types

  • Clinical Trial Protocol
  • Multicenter Study

MeSH terms

  • COVID-19* / complications
  • Clinical Trials, Phase II as Topic*
  • Cognition
  • Cognitive Behavioral Therapy / methods
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / psychology
  • Cognitive Dysfunction* / therapy
  • Humans
  • Multicenter Studies as Topic*
  • Post-Acute COVID-19 Syndrome
  • Prospective Studies
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • SARS-CoV-2*
  • Transcranial Direct Current Stimulation
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT05965739