Long COVID Brain Fog: Cognitive Rehabilitation Trial

NCT ID: NCT06095297

Last Updated: 2025-07-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-25

Study Completion Date

2027-04-30

Brief Summary

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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

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Conditions

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Long COVID Brain Fog Cognitive Impairment Cognitive Dysfunction Post-Acute COVID-19 Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The tester will masked to group assignment.

Study Groups

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CICT

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.

Group Type EXPERIMENTAL

Processing Speed Training

Intervention Type BEHAVIORAL

Speed of processing training involves trainer-guided practice of computer-based video "games." The games require the "player" to rapidly distinguish targets from decoys, which trains how rapidly the player processes information received through their senses.

In-lab Instrumental Activities of Daily Living Training

Intervention Type BEHAVIORAL

Participant will receive shaping on IADLS. Participants will receive training on everyday tasks with important cognitive components, in which the difficulty is increased in small steps over the course of treatment.

Transfer Package

Intervention Type BEHAVIORAL

The Transfer Package was designed to try and bridge the gap between what is trained in the lab and what the participant does outside of the treatment setting. This components includes negotiation of a behavioral contract with participants at the outset of treatment regarding the responsibilities of the participant, family caregivers, if available, and the treatment team, self-monitoring, assignment of "homework," review of homework by the trainer, and support of problem-solving by the participant.

Follow Up Phone Calls

Intervention Type BEHAVIORAL

After completing training, participants will receive four follow up phone calls in the first month of training. Each call will separated by about a week. The focus of the calls will incorporating the lessons learnt during treatment into daily life.

Trans-auricular Vagus Nerve Stimulation: High Intensity

Intervention Type PROCEDURE

The vagus nerve run from the brain to the external ear, throat, chest, and abdomen and controls, among other functions, the rest and relax response, which supports learning and turns down inflammatory processes. The rest and relax response can be turned on by electrically stimulating the vagus nerve. We will place electrodes on the external part of each ear and safely apply a microcurrent of at least 4 milliamps. Stimulation will administered for 10 minutes near the start and midway point of each treatment session.

CICT + VR

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.

Group Type EXPERIMENTAL

Processing Speed Training

Intervention Type BEHAVIORAL

Speed of processing training involves trainer-guided practice of computer-based video "games." The games require the "player" to rapidly distinguish targets from decoys, which trains how rapidly the player processes information received through their senses.

In-lab Instrumental Activities of Daily Living Training

Intervention Type BEHAVIORAL

Participant will receive shaping on IADLS. Participants will receive training on everyday tasks with important cognitive components, in which the difficulty is increased in small steps over the course of treatment.

Transfer Package

Intervention Type BEHAVIORAL

The Transfer Package was designed to try and bridge the gap between what is trained in the lab and what the participant does outside of the treatment setting. This components includes negotiation of a behavioral contract with participants at the outset of treatment regarding the responsibilities of the participant, family caregivers, if available, and the treatment team, self-monitoring, assignment of "homework," review of homework by the trainer, and support of problem-solving by the participant.

Follow Up Phone Calls

Intervention Type BEHAVIORAL

After completing training, participants will receive four follow up phone calls in the first month of training. Each call will separated by about a week. The focus of the calls will incorporating the lessons learnt during treatment into daily life.

Vocational Rehabilitation

Intervention Type BEHAVIORAL

In partnership with the Alabama Department of Rehabilitation Services (ADRS), participants who are eligible may receive vocational rehabilitation. Participants will receive typical services offered by the ADRS. These could include career counseling, guidance regarding job retention or return-to-work, and guidance regarding workplace accommodations.

Peer Mentoring

Intervention Type BEHAVIORAL

Participants who are eligible for vocational rehabilitation, and agree will also have a peer mentor, a co-worker that will be trained by our team, to reinforce strategies the participant learned during training, and to help the participant problem solve issues that may arise on the job during the first month after treatment. Peer mentors will meet with trainers during the month after treatment to make sure procedures are being followed and address any issues that may arise.

Trans-auricular Vagus Nerve Stimulation: High Intensity

Intervention Type PROCEDURE

The vagus nerve run from the brain to the external ear, throat, chest, and abdomen and controls, among other functions, the rest and relax response, which supports learning and turns down inflammatory processes. The rest and relax response can be turned on by electrically stimulating the vagus nerve. We will place electrodes on the external part of each ear and safely apply a microcurrent of at least 4 milliamps. Stimulation will administered for 10 minutes near the start and midway point of each treatment session.

BFT

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.

Group Type ACTIVE_COMPARATOR

In-lab Brain Health Training

Intervention Type BEHAVIORAL

Participants will receive training on healthy eating, sleeping, and relaxation techniques that have been shown to improve brain health.

Transfer Package

Intervention Type BEHAVIORAL

The Transfer Package was designed to try and bridge the gap between what is trained in the lab and what the participant does outside of the treatment setting. This components includes negotiation of a behavioral contract with participants at the outset of treatment regarding the responsibilities of the participant, family caregivers, if available, and the treatment team, self-monitoring, assignment of "homework," review of homework by the trainer, and support of problem-solving by the participant.

Follow Up Phone Calls

Intervention Type BEHAVIORAL

After completing training, participants will receive four follow up phone calls in the first month of training. Each call will separated by about a week. The focus of the calls will incorporating the lessons learnt during treatment into daily life.

Reaction Time Training

Intervention Type BEHAVIORAL

Reaction time training involves trainer-guided practice of computer-based video "games." Several different games will be featured that train how rapidly "players" react to "threats" and train eye-hand coordination.

Trans-auricular Vagus Nerve Stimulation: Low Intensity

Intervention Type PROCEDURE

The vagus nerve run from the brain to the external ear, throat, chest, and abdomen and controls, among other functions, the rest and relax response, which supports learning and turns down inflammatory processes. The rest and relax response can be turned on by electrically stimulating the vagus nerve. We will place electrodes on the external part of each ear and safely apply a microcurrent of less than 4 milliamps. Stimulation will administered for 10 minutes near the start and midway point of each treatment session.

BFT + VR

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.

Group Type ACTIVE_COMPARATOR

In-lab Brain Health Training

Intervention Type BEHAVIORAL

Participants will receive training on healthy eating, sleeping, and relaxation techniques that have been shown to improve brain health.

Transfer Package

Intervention Type BEHAVIORAL

The Transfer Package was designed to try and bridge the gap between what is trained in the lab and what the participant does outside of the treatment setting. This components includes negotiation of a behavioral contract with participants at the outset of treatment regarding the responsibilities of the participant, family caregivers, if available, and the treatment team, self-monitoring, assignment of "homework," review of homework by the trainer, and support of problem-solving by the participant.

Follow Up Phone Calls

Intervention Type BEHAVIORAL

After completing training, participants will receive four follow up phone calls in the first month of training. Each call will separated by about a week. The focus of the calls will incorporating the lessons learnt during treatment into daily life.

Vocational Rehabilitation

Intervention Type BEHAVIORAL

In partnership with the Alabama Department of Rehabilitation Services (ADRS), participants who are eligible may receive vocational rehabilitation. Participants will receive typical services offered by the ADRS. These could include career counseling, guidance regarding job retention or return-to-work, and guidance regarding workplace accommodations.

Reaction Time Training

Intervention Type BEHAVIORAL

Reaction time training involves trainer-guided practice of computer-based video "games." Several different games will be featured that train how rapidly "players" react to "threats" and train eye-hand coordination.

Trans-auricular Vagus Nerve Stimulation: Low Intensity

Intervention Type PROCEDURE

The vagus nerve run from the brain to the external ear, throat, chest, and abdomen and controls, among other functions, the rest and relax response, which supports learning and turns down inflammatory processes. The rest and relax response can be turned on by electrically stimulating the vagus nerve. We will place electrodes on the external part of each ear and safely apply a microcurrent of less than 4 milliamps. Stimulation will administered for 10 minutes near the start and midway point of each treatment session.

Interventions

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Processing Speed Training

Speed of processing training involves trainer-guided practice of computer-based video "games." The games require the "player" to rapidly distinguish targets from decoys, which trains how rapidly the player processes information received through their senses.

Intervention Type BEHAVIORAL

In-lab Instrumental Activities of Daily Living Training

Participant will receive shaping on IADLS. Participants will receive training on everyday tasks with important cognitive components, in which the difficulty is increased in small steps over the course of treatment.

Intervention Type BEHAVIORAL

In-lab Brain Health Training

Participants will receive training on healthy eating, sleeping, and relaxation techniques that have been shown to improve brain health.

Intervention Type BEHAVIORAL

Transfer Package

The Transfer Package was designed to try and bridge the gap between what is trained in the lab and what the participant does outside of the treatment setting. This components includes negotiation of a behavioral contract with participants at the outset of treatment regarding the responsibilities of the participant, family caregivers, if available, and the treatment team, self-monitoring, assignment of "homework," review of homework by the trainer, and support of problem-solving by the participant.

Intervention Type BEHAVIORAL

Follow Up Phone Calls

After completing training, participants will receive four follow up phone calls in the first month of training. Each call will separated by about a week. The focus of the calls will incorporating the lessons learnt during treatment into daily life.

Intervention Type BEHAVIORAL

Vocational Rehabilitation

In partnership with the Alabama Department of Rehabilitation Services (ADRS), participants who are eligible may receive vocational rehabilitation. Participants will receive typical services offered by the ADRS. These could include career counseling, guidance regarding job retention or return-to-work, and guidance regarding workplace accommodations.

Intervention Type BEHAVIORAL

Peer Mentoring

Participants who are eligible for vocational rehabilitation, and agree will also have a peer mentor, a co-worker that will be trained by our team, to reinforce strategies the participant learned during training, and to help the participant problem solve issues that may arise on the job during the first month after treatment. Peer mentors will meet with trainers during the month after treatment to make sure procedures are being followed and address any issues that may arise.

Intervention Type BEHAVIORAL

Reaction Time Training

Reaction time training involves trainer-guided practice of computer-based video "games." Several different games will be featured that train how rapidly "players" react to "threats" and train eye-hand coordination.

Intervention Type BEHAVIORAL

Trans-auricular Vagus Nerve Stimulation: High Intensity

The vagus nerve run from the brain to the external ear, throat, chest, and abdomen and controls, among other functions, the rest and relax response, which supports learning and turns down inflammatory processes. The rest and relax response can be turned on by electrically stimulating the vagus nerve. We will place electrodes on the external part of each ear and safely apply a microcurrent of at least 4 milliamps. Stimulation will administered for 10 minutes near the start and midway point of each treatment session.

Intervention Type PROCEDURE

Trans-auricular Vagus Nerve Stimulation: Low Intensity

The vagus nerve run from the brain to the external ear, throat, chest, and abdomen and controls, among other functions, the rest and relax response, which supports learning and turns down inflammatory processes. The rest and relax response can be turned on by electrically stimulating the vagus nerve. We will place electrodes on the external part of each ear and safely apply a microcurrent of less than 4 milliamps. Stimulation will administered for 10 minutes near the start and midway point of each treatment session.

Intervention Type PROCEDURE

Other Intervention Names

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In-lab IADL Training In-lab Stress Management Training TP

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Disability, Independent Living, and Rehabilitation Research

FED

Sponsor Role collaborator

Posit Science

UNKNOWN

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Gitendra Uswatte

Professor of Psychology & Physical Therapy

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gitendra Uswatte, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor of Psychology, University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Madeline Rathz, BS

Role: CONTACT

205-934-9768

Staci McKay, BS

Role: CONTACT

205-934-9768

Facility Contacts

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Piper Hempfling, MS

Role: primary

205-934-9768

Staci McKay, BS

Role: backup

205-934-9768

Other Identifiers

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90IFRE0073

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB-300010908

Identifier Type: -

Identifier Source: org_study_id

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