Control Network Neuromodulation to Enhance Cognitive Training in Complex Traumatic Brain Injury
CONNECT-TBI
1 other identifier
interventional
108
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Jan 2022
Longer than P75 for not_applicable
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 21, 2022
CompletedFirst Submitted
Initial submission to the registry
February 1, 2022
CompletedFirst Posted
Study publicly available on registry
February 11, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2026
May 26, 2026
May 1, 2026
4.4 years
February 1, 2022
May 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Primary symptom outcome: Change from baseline in cognitive PCS as measured by the NSI cognitive subscale score at post-treatment.
Post-concussive symptoms will be measured with the Neurobehavioral Symptom Inventory (NSI). This assessment will be administered at the baseline and post-treatment visits. The NSI is a self-report questionnaire that consists of 22 non-specific complaints commonly reported after concussion and is used to quantify traumatic brain injury (TBI) symptom severity and select symptoms for treatment. The NSI asks the patient to rate each of the symptoms according to how much the symptom has disturbed him/her using a five point scale. Patient ratings are based on descriptions of the frequency of the symptom, the extent to which the symptom disrupts the patient's activities, and the patient's perceived need for help with the symptom. The 22 individual symptoms items are weighted equally. The cognitive subscale score uses 4 items, where a higher score means more severe symptoms and a lower score means less severe symptoms. The minimum value is 0, and the maximum value is 16
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.
The MMWM is a continuous performance test in which subjects respond to simultaneous sequences of visual (squares on a grid) and auditory (spoken numbers) stimuli by pressing a button if stimuli in either or both sensory modalities match a previous stimulus (1-back or 2-back).
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.
The Patient Global Impression of Change (PGIC) is a self-report scale that reflects a patient's belief about the efficacy of treatment. The PGIC is a 7 point scale depicting a patient's rating of overall improvement, where a 1 is no change and a 7 is a great deal of change.
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.
The blood oxygen level-dependent (BOLD) signal will be measured during the MMWM task performance to determine correlation with symptom improvement on NSI. The BOLD signal will be measured at the baseline and post-treatment MRIs.
Baseline and post-treatment visits, 4 weeks
Study Arms (4)
Active rTMS with Attention Process Training
ACTIVE COMPARATORSubjects in this arm will receive active rTMS and then complete the assigned Attention Process Training battery immediately following active rTMS.
Sham rTMS with Attention Process Training
SHAM COMPARATORSubjects in this sham arm will not receive any active stimulation and will only complete Attention Process Training immediately following sham rTMS.
Active HD-tDCS with Attention Process Training
ACTIVE COMPARATORSubjects in this arm will receive active HD-tDCS and complete the assigned Attention Process Training battery during active HD-tDCS.
Sham HD-tDCS with Attention Process Training
SHAM COMPARATORSubjects in this sham arm will not receive any active stimulation and will only complete Attention Process Training during sham HD-tDCS.
Interventions
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.
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 (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.
Eligibility Criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of New Mexicolead
- The Mind Research Networkcollaborator
- New Mexico VA Healthcare Systemcollaborator
- Minneapolis Veterans Affairs Medical Centercollaborator
- University of Minnesotacollaborator
Study Sites (5)
Minneapolis Veterans Affairs Medical Center
Minneapolis, Minnesota, 55417, United States
The University of Minnesota
Minneapolis, Minnesota, 55455, United States
The Mind Research Network
Albuquerque, New Mexico, 87106, United States
The University of New Mexico
Albuquerque, New Mexico, 87106, United States
New Mexico Veterans Affairs Health Care System
Albuquerque, New Mexico, 87108, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Davin k Quinn, MD, FACLP
University of New Mexico
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Psychiatry, Vice Chair and Quality/Safety Officer, Adult Clinical Services, Chief, Division of Behavioral Health Consultation and Integration, Director, Transcranial Magnetic Stimulation Service
Study Record Dates
First Submitted
February 1, 2022
First Posted
February 11, 2022
Study Start
January 21, 2022
Primary Completion (Estimated)
July 1, 2026
Study Completion (Estimated)
July 1, 2026
Last Updated
May 26, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- The data submission schedule for United States Department of Defense studies in the FITBIR system is once per year (March or September). Data will be available indefinitely.
- Access Criteria
- Six months after submission of data, the Core (required) and Basic (recommended) TBI common data elements (CDEs) that are used in the study will be made available to all qualified and approved researchers (Data Access Account holders) as determined by the Data Access Committee (DAC). Data Access Account holders will be referred to as "Recipients". Other data fields can also be made available at the submitting principal investigator's discretion. Data Submission Account holders will be referred to as "Submitter's". Outcomes data and other data elements needed by the principal investigator to test his/her hypotheses or research questions, referred to as Experimental Data, will be made available in a staged manner. Six months after the award period ends, Experimental Data will be open to other researchers who have submitted data to FITBIR (Submitters). Twelve months after the award period ends, Experimental Data will be open to all qualified and approved researchers (Recipients).
In accordance with the guidelines for research conducted in the field of traumatic brain injury (TBI), and in the interests of sharing and leveraging data and research resources, and avoiding duplication of efforts, Co-PIs Quinn and Davenport will make data generated by the performance of the planned clinical trial available to the research community by depositing the de-identified data into the Federal Interagency TBI Research (FITBIR) Informatics system. All data collected on study evaluations and questionnaires will be shared and uploaded to FITBIR. This includes demographic data, diagnostic assessment data (medical history, medications, combat exposure, screening for traumatic brain injury, neurological assessments, post-traumatic epilepsy assessments, neuropsychiatric diagnostic assessments), symptomatic and functional status assessment data (neurobehavioral symptoms, PTSD symptoms, depression symptoms, quality of life assessments), cognitive testing data, and fMRI imaging data.