ME/CFS Brain Fog: Cognitive Rehabilitation Trial

Summary

The purpose of this study is to compare two approaches to cognitive rehabilitation in adults with post-viral cognitive syndrome, which resulted in brain fog. All participants will be screened for eligibility prior to participation. Most of the procedures will take place over a phone call or secure telehealth platform (i.e., Zoom). However, participants will be asked to visit UAB on three occasions for blood sample collection and brain imaging (about 2 hours each). Online testing will happen one month before treatment, one day before treatment, one day afterwards, and 6 months afterwards. The study will utilize two different forms of rehabilitation training to improve participants' cognitive ability. Participants will be randomized to one of the two treatment groups. The first treatment approach, known as Constraint-Induced Cognitive Therapy (CICT), will feature (A) web-based computer "games" that trains how quickly individuals process information that they receive through their senses; (B) online 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, also known as trans-auricular VNS (taVNS). The second approach, known as Brain Fitness Training (BFT), will include (A) web-based computer "games" that train reaction time and eye-hand coordination; (B) in-lab training on relaxation, breathing, healthy nutrition, and healthy sleep, (C) education about how relaxation, breathing, nutrition, and sleep are connected to thinking effectiveness, and (D) taVNS. Approximately 30 hours of training will be conducted over a secure telehealth platform (i.e., Zoom) in the span of two- to four- weeks. A typical CICT session will consist of one hour of gaming, with the bulk of the session being spent on cognitive training of the target behaviors and procedures designed to promote transfer of therapeutic gains to daily life. ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. A typical BFT session will consist of one hour of gaming, training on healthy lifestyle behaviors (i.e., healthy sleep, nutrition, and relaxation habits), as well as procedures designed to promote transfer of behavior changes to daily life. Ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. Training sessions in both conditions will be scheduled based on participants' availability, with the options for sessions scheduled to be as close as every weekday over 2 weeks or as loosely as every other weekday (i.e., over a 4-week span). If a caregiver is available, they will receive training on how to best support participants in their therapeutic program. After the training ends, both groups will receive 4 follow-up phone calls approximately one week apart to promote integration of the gained skills into everyday life. 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.

Conditions

• ME/CFS
• ME/CFS Following EBV-associated Infectious Mononucleosis
• ME/CFS Following COVID-19
• Chronic Fatigue
• Chronic Fatigue Syndrome (CFS)
• Brain Fog
• Cognitive Impairment
• Cognitive Dysfunction

Interventions

BEHAVIORAL

Transfer Package

The Transfer Package was designed to try to bridge the gap between what is trained in-session and what the participant does outside of treatment sessions. These components include 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.

BEHAVIORAL

Follow Up Phone Calls

After completing training, participants will receive four weekly follow-up phone calls in the first month of training. The focus of the calls will incorporate the lessons learnt during treatment into daily life.

PROCEDURE

Trans-auricular Vagus Nerve Stimulation: High Intensity

The vagus nerve runs 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 activated 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 be administered for 10 minutes near the start and midway point of each treatment session.

BEHAVIORAL

In-session Brain Health Training

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

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.

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.

BEHAVIORAL

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 the player to process information from their senses quickly.

BEHAVIORAL

In-session Instrumental Activities of Daily Living Training

Participants 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.

Sponsors & Collaborators

• UAB College of Arts and Sciences & Department of Psychology

  collaborator UNKNOWN

• Posit Science Corporation

  collaborator INDUSTRY

• University of Alabama at Birmingham

  lead OTHER

Principal Investigators

• Gitendra Uswatte, PhD · Professor of Psychology, University of Alabama at Birmingham

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-04-30

Primary Completion

2026-04-30

Completion

2028-04-30

Countries

• United States

Study Locations