Recruiting

CICT & BFT

Sponsor:

University of Alabama at Birmingham

Code:

NCT07523113

Conditions

ME/CFS

ME/CFS Following EBV-associated Infectious Mononucleosis

ME/CFS Following COVID-19

Chronic Fatigue

Chronic Fatigue Syndrome (CFS)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Processing Speed Training

In-session Instrumental Activities of Daily Living Training

Transfer Package

Follow Up Phone Calls

Trans-auricular Vagus Nerve Stimulation: High Intensity

Study Details

Brief 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)

Study ID

NCT07523113

Start date

Jun 23, 2026

Status verified date

Aug, 2026

Completion date

Jun, 2028

Anticipated

Primary completion date

Jun, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • diagnosis of ME/CFS that preceded cognitive complaints
  • mild or greater cognitive impairment
  • moderate or greater brain fog
  • some impairment in the performance of daily activities
  • ≥ 18 years, no upper limit if medically stable
  • reside in the community (as opposed to a hospital or skilled nursing facility)
  • able to travel to the laboratory on multiple occasions
  • has Internet service
  • has a personal computer, laptop, or tablet that can access the Internet
  • sufficiently fit, from both a physical and mental health perspective, to take part in the study
  • adequate sight and hearing to complete the UFOV test
  • adequate thinking skills, e.g., ability to follow directions and retain information to complete UFOV and CTAL, as marked by the judgement of the screener that the candidate is able to adequately complete the UFOV and CTAL
  • sufficient English proficiency (i.e., ability to speak, understand, read, and write to take part in study activities)

Exclusion Criteria:

  • cognitive impairment due to a developmental disability, psychiatric disorder, or substance abuse, or due to another type of brain injury, such as traumatic brain injury, stroke, or a progressive brain disease, such as Alzheimer's Dementia
  • current substance abuse disorder
  • diagnosis of postural orthostatic tachycardia syndrome (POTS) by a healthcare provider
  • prior cognitive processing speed training on DoubleDecision or a similar program
  • cannot tolerate taVNS
  • prior history of heart attack or other serious cardiac events
  • implanted medical device of any type
  • vasovagal syncope or history of fainting
  • history of seizures or epilepsy
  • temporomandibular Joint (TMJ) syndrome or other conditions that cause substantial jaw pain
  • history of peripheral nerve injury to the head, neck, or face
  • pregnant or breastfeeding
  • not able or willing to get an MRI scan
  • not able or willing to get a blood draw

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: CICT + taVNS

Constraint-Induced Cognitive Therapy uses in-lab training on everyday activities with important cognitive components, along with the procedures designed to transfer improvements from the treatment setting to everyday life. This will be combined with computer-based processing speed training and non-invasive vagus nerve stimulation.

active comparator: BFT + taVNS

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.

Interventions

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.

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.

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.

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.

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.

In-session Brain Health Training

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

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.

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.

Primary outcome measure

  • Canadian Occupational Performance Measure (COPM) [ Time Frame: Change from Day 30 to Day 60 (i.e., change from Pre- to Post-treatment) ]

Central Contacts and Locations

Central contacts

Madeline Rathz, BS

205-934-9768mgrathz@uab.edu

Helen Bliss, BS

205-934-0433hmbliss@uab.edu

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

Contacts

Natalie Greig, BS

205-934-9768nggreig@uab.edu

Helen Bliss, BS

205-934-0433hmbliss@uab.edu

Principal Investigator:

Gitendra Uswatte, PhD

More Information

Sponsor

University of Alabama at Birmingham

Last update posted

Aug 14, 2026

Last verified

Aug, 2026

Keywords

  • ME/CFS
  • Chronic Fatigue
  • Brain fog
  • Cognitive Impairment
  • Cognitive Dysfunction
  • post-viral syndrome
  • Cognitive Rehabilitation
  • CICT

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-03. This information was provided to ClinicalTrials.gov by University of Alabama at Birmingham on 2026-08-14. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.