Cognitive Rehabilitation Therapy for COVID-19

Study Overview
=================
Brief Summary
-----------------
Cognitive dysfunction, psychiatric symptoms, functional impairment, and disability following COVID-19 negatively impact Veterans' community functioning and quality of life, contribute to significant human suffering, and are costly to VHA. Rehabilitation is a critical priority for Veterans with long COVID. One promising treatment to improve functioning in Veterans with post-COVID-19 cognitive symptoms is Compensatory Cognitive Training (CCT). Previous studies have found that CCT is feasible, acceptable, and efficacious in Veteran populations with multiple sources of cognitive dysfunction. This randomized controlled trial aims to address important RR&D priorities by examining feasibility, acceptability, and preliminary efficacy of a COVID-19-specific rehabilitation intervention, CCT for long COVID (CCT-C) compared to a robust control condition. The proposed study has the potential to improve cognitive function, functional independence, and quality of life for Veterans with late or delayed effects of secondary conditions related to COVID-19 infections.

Detailed Description
-----------------
2-8% of the US population report long COVID symptoms - including brain fog, thinking difficulties, memory problems, and psychiatric symptoms such as sleep disturbance, anxiety, and depression. Rates of post-COVID-19 symptoms are nearly double in the Veteran population. These cognitive symptoms contribute to functional impairments, reduced quality of life, poorer self-reported health status, psychological distress, delayed return to work, new onset disability, reduced community integration, and increased healthcare utilization. One promising treatment to improve both everyday functioning and cognition secondary to post-COVID-19 symptoms is Compensatory Cognitive Training (CCT). Previous studies have found that CCT is feasible, acceptable, and efficacious in Veteran populations with multiple sources of cognitive dysfunction. The proposed CDA provides a golden opportunity to evaluate CCT for Veterans with prolonged COVID-19 symptoms (CCT-C), compared with a robust control condition, Holistic Cognitive Education (HCE). The project closely aligns with current RR&D priorities, by examining COVID-19-specific rehabilitation interventions and responses to treatment and by addressing late or delayed effects of secondary conditions related to COVID-19 infections on impairment and disability. Specific aims are 1) to conduct a pilot randomized controlled trial of remote CCT-C with 70 Veterans (35 CCT-C, 35 HCE) with post-COVID-19 cognitive symptoms to examine feasibility, acceptability, and initial efficacy; 2) to examine the preliminary efficacy of CCT-C in this population on overall functioning, as measured by the World Health Organization's Disability Assessment Schedule (WHODAS 2.0), performance-based measures of functional capacity, and secondary outcomes (cognitive performance, quality of life, self-reported cognitive problems, psychiatric symptoms, sleep disturbance, and engagement in work/community activities); and 3) to explore moderators of outcome (e.g., age, initial COVID-19 severity, baseline cognitive functioning, presence of PTSD/mTBI history; biomarkers related to COVID-19 infection).

Official Title
-----------------
Cognitive Rehabilitation to Improve Functioning in Veterans Following COVID-19

Conditions
-----------------
Post-Acute COVID-19 Syndrome

Intervention / Treatment
-----------------
* Behavioral: Compensatory Cognitive Training for COVID-19
* Behavioral: Holistic Cognitive Education


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Veterans > 18 years old who are able to provide informed consent Prior participation in SF Parent Study or LA Parent Study Report of cognitive symptoms that Veteran attributes to COVID-19 infection Exclusion Criteria: Current substance abuse disorder, psychotic disorder, dementia, etc. History of moderate to severe brain injury with loss of consciousness > 30 minutes Auditory or visual impairments that would prevent the ability to participate in assessment procedures Invalid performance on one or more embedded performance validity tests (PVTs)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two group randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCT-C<br>10-week Compensatory Cognitive Training Group | Behavioral: Compensatory Cognitive Training for COVID-19<br>* CCT-C is a manualized group-based behavioral intervention (10 weeks, 2 hours per week, 20 hours total) designed to improve cognition and everyday functioning in patients with prolonged COVID-19 symptoms<br>* Other names: CCT-C;|
| Active Comparator: HCE<br>10-week Holistic Cognitive Education Group | Behavioral: Holistic Cognitive Education<br>* HCE provides the same frequency and amount of therapist and other group member contact as CCT-C, but does not provide training in cognitive or lifestyle strategies addressed in CCT-C. The HCE intervention provides information and discussion regarding common causes of and treatments for cognitive impairment.<br>* Other names: HCE;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in World Health Organization - Disability Assessment Schedule (WHODAS 2.0) | Change in average total score | baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in objective cognitive performance z score | Change in composite z score | baseline, 8 weeks | 
| Change in functional capacity performance z score | Change in composite z score | baseline, 8 weeks | 
| Change in Patient Health Questionnaire 9 (PHQ-9) | Change in total score | baseline, 8 weeks | 
| Change in Generalized Anxiety Disorder 7 (GAD-7) | Change in total score | baseline, 8 weeks | 
| Change in PTSD Checklist for DSM-5 (PCL-5) | Change in total score | baseline, 8 weeks | 
| Change in Cognitive Failures Questionnaire (CFQ) | Change in total score | baseline, 8 weeks | 
| Change in Neuro-QOL: Applied Cognition General Concerns | Change in total score | baseline, 8 weeks | 
| Change in Neuro-QOL: Applied Cognition Executive Functioning | Change in total score | baseline, 8 weeks | 
| Change in Neuro-QOL: Fatigue | Change in total score | baseline, 8 weeks | 
| Change in World Health Organization - Quality of Life (WHOQOL-BREF) | Change in total score | baseline, 8 weeks | 
| Change in Insomnia Severity Index (ISI) | Change in total score | baseline, 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Post-Acute COVID-19 Syndrome, Cognitive rehabilitation, Cognitive training, Cognitive remediation