ME/CFS Brain Fog: Cognitive Rehabilitation Trial

Official title

Brain Training for Chronic, Post-viral, Brain Fog: Study A

Overview

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.

Interventions

• 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.
• 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
• 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 ea

Primary outcome measures

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Alabama at Birmingham — Birmingham

Identifiers

NCT: NCT07523113 · IRB-300015629 · UAB CAS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗