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.
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Parallel
rTMS
DeviceTranscranial 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
DeviceTranscranial 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
Other interventionAttention 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 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
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).
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.
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.
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University of New Mexico
Lead sponsor
The Mind Research Network
Collaborator
New Mexico VA Healthcare System
Collaborator
Minneapolis Veterans Affairs Medical Center
Collaborator
University of Minnesota
Collaborator
