Recruiting

Neuromodulation

Sponsor:

University of New Mexico

Code:

NCT05236010

Conditions

Traumatic Brain Injury

Eligibility Criteria

Sex: All

Age: 18 - 59

Healthy Volunteers: Not accepted

Interventions

rTMS

HD-tDCS

Attention Process Training

Study Details

Brief summary:

The CONNECT-TBI Trial aims to develop safe, effective treatments for complex mTBI that improve cognitive functioning. Based on the compelling preliminary data generated by our study team, the objective of this study is to conduct a randomized, double-blinded, sham-controlled Phase II clinical trial of APT-3 combined with rTMS, HD-tDCS, or sham to treat cognitive control deficits in Veterans with complex mTBI and PPCS. At the Baseline Visit, participants will undergo demographic, neuropsychological, behavioral, and quality of life testing. They will also undergo structural MRI to permit modeling of their brain, resting/task-related fMRI to identify the CCN, and pseudocontinuous arterial spin labeling (pCASL) and diffusion tensor imaging (DTI) to assess for other pathologies. They will then be randomized to 16 sessions of APT-3 with concurrent rTMS, HD-tDCS, or sham stimulation delivered to the unique functional left dorsolateral prefrontal cortex (DLPFC), a primary node of the CCN. Lastly, they will repeat all baseline tests, and report on 3- and 6-month recovery levels to establish longevity and stability of subjective benefit. Given that this individualization protocol has never been attempted for cognitive rehabilitation in military mTBI, we expect this trial will generate useful effect sizes for HD-tDCS and rTMS to be used for powering the next step, a Phase III multi-center trial.

Conditions

Traumatic Brain Injury

Study ID

NCT05236010

Start date

Jan 21, 2022

Status verified date

Aug, 2026

Completion date

Oct 1, 2026

Anticipated

Primary completion date

Oct 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 59

Healthy Volunteers: Not accepted

Inclusion Criteria:

There will be no gender restrictions with regard to sample inclusion. Veterans and Warfighters will be enrolled in this study if they 1) are aged 18-59; 2) have suffered a mild TBI with documented evidence of alteration in neurological functioning or loss of consciousness (LOC) which was less than 30 minutes; 3) were injured between 3 months and 5 years ago; 4) experienced less than 24 hours of post-traumatic amnesia (PTA); 5) have subjective post-TBI cognitive deficits as assessed by the NSI, with at least 1 of 4 cognitive symptoms at a score of 3 or higher (severe disturbance) or at least 2 of 4 cognitive symptoms at a score of 2 or higher (moderate disturbance). This is the target population as identified by the grant mechanism, with chronic cognitive impairments from mild traumatic brain injury. The age range of 18-59 years was selected because the investigators did not want to include developmental processes in analyses and by 18 years old, many major neurodevelopmental changes in the brain will have taken place. Using similar rationale, the investigators chose to include participants up to the age of 59 because they do not want to include advancing age-related brain changes in our analyses. They will also be 6) fluent in English, as the testing and intervention are all conducted in English; and 7) will have been on stable doses of any psychotropic medications for the past 2 months, so as to avoid confounding of results by medication effects. It is expected that the sample included in this study will reflect the demographics of the greater Albuquerque and Twin Cities metropolitan communities.

Exclusion Criteria:

Veterans will be excluded from participation in this study if there is 1) a prior history of other neurological disease or any history of seizures beyond immediate post-traumatic seizure, so as to reduce risk of exacerbation of epilepsy or other neurological symptoms; 2) history of psychosis, so as to reduce risk of psychiatric decompensation; 3) history of current or recent (within two years) substance/alcohol dependence, to reduce confounding effects on cognition; 4) any discontinuity in skull electrical conductivity (i.e., unhealed burr holes in scalp) or artificially constructed (metal or plastic) craniotomy cover, to reduce risk of unimpeded electrical current; 5) presence of any implanted metal or electrical device (e.g. pacemaker), to reduce risk of heating during MRI, or device malfunction during neuromodulation; 6) recent medical hospitalization (within three weeks), to reduce risk of medical decompensation during the study; 7) any condition that would prevent the participant from completing the protocol, such as significant agitation; 8) appointment of a legal representative, as assessed via direct inquiry of the participant or a designated trusted other, to avoid coercion of a vulnerable population; 9) any significant hardness of hearing or blindness that would make completing the cognitive training not possible; 10) any ongoing litigation related to TBI, to prevent interference with legal proceedings; 11) any other contraindication to exposure to strong magnetic fields or MRI, such as severe claustrophobia; 12) pregnant women will be excluded as the effects of MRI and brain stimulation on developing fetuses are unknown; 13) membership in an identified vulnerable population, including minors, and prisoners, and adults unable to consent due to cognitive impairment will be excluded, as they will be unlikely to be able to complete study procedures. Prisoners will be excluded from the study to avoid coercion; 14)received a Glasgow coma scale (GCS) less than 13 or greater than 15 upon ED admission, if available in patient's records.

The investigators do not intend to include adults who are unable to consent in this study.

The investigators do not intend to include individuals who are not yet adults (infants, children, teenagers) in this study.

The investigators do not intend to include pregnant women in this study.

The investigators do not intend to include prisoners in this study.

Study Design

Enrollment

108 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Active rTMS with Attention Process Training

Subjects in this arm will receive active rTMS and then complete the assigned Attention Process Training battery immediately following active rTMS.

sham comparator: Sham rTMS with Attention Process Training

Subjects in this sham arm will not receive any active stimulation and will only complete Attention Process Training immediately following sham rTMS.

active comparator: Active HD-tDCS with Attention Process Training

Subjects in this arm will receive active HD-tDCS and complete the assigned Attention Process Training battery during active HD-tDCS.

sham comparator: Sham HD-tDCS with Attention Process Training

Subjects in this sham arm will not receive any active stimulation and will only complete Attention Process Training during sham HD-tDCS.

Interventions

rTMS

Transcranial magnetic stimulation is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. During an rTMS session, an electromagnetic coil is placed against the scalp near the forehead. The electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the region of the brain being targeted.

HD-tDCS

Transcranial direct current stimulation (tDCS), is a non-invasive, painless brain stimulation treatment that uses direct electrical currents to stimulate specific parts of the brain. A constant, low intensity current is passed through two electrodes placed over the head which modulates neuronal activity.

Attention Process Training

Attention Process Training (APT) is a multi-session exercise designed to help improve the ability to focus on relevant material while ignoring irrelevant distractions. Further, it helps improve the speed of processing information.

Primary outcome measure

  • Primary symptom outcome: Change from baseline in cognitive PCS as measured by the NSI cognitive subscale score at post-treatment. [ Time Frame: Baseline and post-treatment visits, 4 weeks ]
  • Primary cognitive outcome: Change from baseline in objective cognitive control as measured by accuracy on the Multi-modal Working Memory N-back task (MMWM) to post-treatment Visit. [ Time Frame: Baseline and post-treatment visits, 4 weeks ]
  • Primary functional outcome: Change from post-treatment visit in overall quality of life as measured by the PGIC at long-term follow-up at 3 and 6 months. [ Time Frame: Post-treatment visit and long-term follow-up at 3 and 6 months ]
  • Primary imaging outcome: Change (decrease) in CCN activity from Baseline Visit to Post-treatment Visit as measured by the BOLD signal during the MMWM task performance. [ Time Frame: Baseline and post-treatment visits, 4 weeks ]

Central Contacts and Locations

Central contacts

Locations

Minneapolis Veterans Affairs Medical Center

Recruiting

Minneapolis, Minnesota, United States, 55417

Contacts

Sloan Davidson, MS

david982@umn.edu

New Mexico Veterans Affairs Health Care System

Recruiting

Albuquerque, New Mexico, United States, 87108

Contacts

More Information

Sponsor

University of New Mexico

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Keywords

  • Traumatic Brain Injury
  • mTBI
  • Prolonged Post Concussive Symptoms
  • Brain Stimulation
  • Cognitive Rehabilitation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of New Mexico on 2026-08-21.