Long COVID Brain Fog: Cognitive Rehabilitation Trial

Not Applicable

Recruiting

• Conditions: Cognitive Impairment; Brain Fog; Post-Acute COVID-19 Syndrome; Long COVID; Cognitive Dysfunction
• Interventions: Behavioral: In-lab Brain Health Training; Behavioral: Processing Speed Training; Behavioral: In-lab Instrumental Activities of Daily Living Training; Behavioral: Transfer Package; Behavioral: Follow Up Phone Calls; Behavioral: Vocational Rehabilitation; Behavioral: Reaction Time Training; Behavioral: Peer Mentoring

• Registration Number: NCT06095297
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

This study will compare two approaches to cognitive rehabilitation in adults with long COVID with persistent, mild to moderate, cognitive impairment. One approach will feature (A) web-based computer "games" that trains how quickly individuals process information that they receive through their senses; (B) in-lab training on everyday activities with important cognitive components, (C) procedures designed to transfer improvements in cognition from the treatment setting to everyday life, and (D) a non-invasive form of vagus nerve stimulation (VNS), i.e., trans-auricular VNS (taVNS). Component B will include work-related tasks. This approach is termed Constraint-Induced Cognitive Therapy (CICT). The other approach will feature (A) web-based computer "games" that train reaction time and eye-hand coordination; (B) in-lab training on relaxation, healthy nutrition, and healthy sleep, (C) procedures designed to promote integration of these lifestyle changes into everyday life, and (D) taVNS. This approach is termed Brain Fitness Training (BFT).

A subset of participants, who qualify for and and desire vocational rehabilitation (VR), will receive VR from the Alabama Department of Rehabilitation Services (ADRS) in addition to CICT or BFT. ADRS VR will include career counseling, prescription of on-the-job accommodations, and guidance on return-to-work. Those in the CICT + VR group will also receive on-the-job coaching from a peer mentor for a month after completing training.

CICT, with or without VR, will involve 30 hours of training. Ten 3-hour in-lab, face-to-face, therapist-directed sessions will be scheduled. These sessions will feature one hour of gaming; the remainder will be committed to in-lab training on the target behaviors and the procedures designed to promote transfer of therapeutic gains to daily life and improving skills essential to work; the set of the latter procedures is termed the Transfer Package. ta-VNS will administered for 10 minutes before gaming and in-lab target behavior training. To accommodate the demands of participants' other activities, training sessions will be permitted to be scheduled as tightly as every weekday over 2 weeks or as loosely as every other weekday or so over 4 weeks. If a family caregiver is available, they will receive training on how to best support participants in their therapeutic program. After training ends, four follow-up phone calls will be scheduled approximately one-week apart with participants to promote integration of the skills gained during training into everyday life.

BFT, with or without VR, will involve 30 hours of training following the same schedule as for CICT. Ten 3-hour in-lab, face-to-face, therapist-directed sessions will be scheduled. These sessions will feature one hour of gaming; the remainder will be committed to in-lab training on the target behaviors (healthy sleep, nutrition and relaxation habits) and the procedures designed to promote transfer of behavior change to daily life. ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. If a family caregiver is available, they will receive training on how to best support participants in their therapeutic program. After training ends, four follow-up phone calls will be scheduled approximately one-week apart with participants to promote integration of the skills gained during training into everyday life.

Participants will be randomly assigned to the interventions. Randomization will be stratified by whether participants qualify for and desire VR from ADRS or not. If yes, participants will be randomized in equal numbers to CICT + VR or BFT + VR. If no, participants will be randomized in equal numbers to CICT or BFT.

Testing will happen one month before treatment, one day before treatment, one day afterwards, and 6-months afterwards. Outcomes measured will include cognitive processing speed, cognitive function on laboratory tests, and spontaneous performance of everyday activities with important cognitive components in daily life. Another important outcome measure will be whether or not participants were able to return back to work or had significant improvements in their work activities.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-19
• Study First Submitted QC: 2023-10-19
• Study First Posted: 2023-10-23
• Study Start: 2024-04-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-23
• Last Update Posted: 2025-05-30
• Primary Completion: 2026-04
• Study Completion: 2027-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• >3 months post COVID
• mild or greater cognitive impairment
• moderate or greater brain fog
• impairment in performance of daily activities
• reside in community
• reliable transportation to lab
• sufficiently mentally and physically fit
• adequate sight and hearing
• ability to follow directions, and retain information
• sufficient English proficiency

Exclusion Criteria

• cognitive impairment due to developmental disability, psychiatric disorder, or substance abuse, TBI or progressive brain disease
• stroke prior to the onset of COVID
• current substance abuse disorder
• prior cognitive processing speed training on DoubleDecision or similar program
• cannot tolerate trans-auricular vagus nerve stimulation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CICT	Follow Up Phone Calls	Constraint-Induced Cognitive Therapy uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation.
CICT + VR	In-lab Instrumental Activities of Daily Living Training	Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
BFT + VR	In-lab Brain Health Training	Brain Fitness Training plus Vocational Rehabilitation involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
CICT + VR	Transfer Package	Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
CICT	Processing Speed Training	Constraint-Induced Cognitive Therapy uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation.
CICT + VR	Peer Mentoring	Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
BFT	In-lab Brain Health Training	Brain Fitness Training involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation.
BFT + VR	Follow Up Phone Calls	Brain Fitness Training plus Vocational Rehabilitation involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
CICT	In-lab Instrumental Activities of Daily Living Training	Constraint-Induced Cognitive Therapy uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation.
CICT	Transfer Package	Constraint-Induced Cognitive Therapy uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation.
BFT + VR	Transfer Package	Brain Fitness Training plus Vocational Rehabilitation involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
BFT + VR	Vocational Rehabilitation	Brain Fitness Training plus Vocational Rehabilitation involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
CICT + VR	Processing Speed Training	Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
CICT + VR	Follow Up Phone Calls	Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
CICT + VR	Vocational Rehabilitation	Constraint-Induced Cognitive Therapy plus Vocational Rehabilitation uses in-lab training on everyday activities with important cognitive components and procedures designed to transfer improvements from the treatment setting to every day life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.
BFT	Follow Up Phone Calls	Brain Fitness Training involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation.
BFT	Transfer Package	Brain Fitness Training involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation.
BFT	Reaction Time Training	Brain Fitness Training involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation.
BFT + VR	Reaction Time Training	Brain Fitness Training plus Vocational Rehabilitation involves in-lab training on relaxation, healthy nutrition, and healthy sleep with procedures designed to promote integration of these lifestyles into everyday life. This will be combined with computer-based reaction time training and non-invasive vagus nerve stimulation. This group will also receive vocational rehabilitation from the Alabama Department of Rehabilitation Services, such as career counseling and building important career skills.

Primary Outcome Measures

Name	Time	Method
Canadian Occupational Performance Measure (COPM)	Change from Day 30 to Day 60, i.e., from Pre- to Post-treatment	The COPM is a standard, validated, trans-diagnostic, patient-centered structured interview which is commonly used to measure the real-world outcome of rehabilitation procedures that span both motor and cognitive functions after stroke. The Performance Scale assesses how well a participant performs five activities in their daily life, i.e., outside the lab, that are important to the participant. Activities, for this purpose, will be restricted to those with an important cognitive component ,i.e., IADL. The 10-point response scale ranges from 1 (not able to do the activity at all) to 10 (able to do the activity extremely well). Performance Scale scores from the participant will be the primary outcome.

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States