Neuromodulation and Neurorehabilitation for mTBI Plus PTSD

Study Overview
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Brief Summary
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This study will determine (i) the magnitude of immediate and sustained effects of a current clinical standard interactive computer attention processing training (APT) when combined with intermittent theta burst stimulation (iTBS), a type of repetitive transcranial magnetic stimulation and (ii) determine how APT + iTBS changes the neurocognitive system of attention in individuals with persistent attention deficits related to mTBI and PTSD.

Official Title
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Neuromodulation and Neurorehabilitation for Treatment of Functional Deficits After mTBI and PTSD

Conditions
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Mild Traumatic Brain Injury, Post Traumatic Stress Disorder

Intervention / Treatment
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* Device: real iTBS
* Behavioral: real APT
* Behavioral: placebo APT
* Device: placebo iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age and no older than 60 years of age 3 months to 10 years post exposure to mTBI event Have co-occurring mTBI and PTSD as defined by the Symptom Attribution and Classification Algorithm (SACA) and the Clinically Administered PTSD Scale for DSM-V (CAPS-5) Exclusion Criteria: Participating in another research study Non-fluent in English (speaking and reading) History of epilepsy pre-injury Receiving antiepileptic treatment for documented active seizures in the past 6 months Taking medications that lower seizure threshold including antipsychotics, buproprion, trazodone and tramadol History of surgery on blood vessels in brain and/or valves of the heart History of brain hemorrhage, neurovascular conditions and neurodegenerative disorders History or current diagnosis of psychotic spectrum disorders (i.e. bipolar, schizophrenia) Significant heart disease as determined by physician review of medical chart Pregnant at time of enrollment or any time during study participation MRI or TMS/iTBS contraindications such as claustrophobia, metal in eyes/face or brain Cardiac pacemakers/defibrillators, cochlear implants, nerve stimulators, intracranial metal clips Diagnosis of moderate or severe TBI (loss of consciousness > 30 minutes, alteration of consciousness > 24 hours, post traumatic amnesia or neuropsychological testing results Mental health medications have been altered within the month preceding study screening Taking prescribed CNS stimulants and choosing to not stop these medications during study participation Testing positive for opiates and do not have a prescription for opiates. If on prescription opiates and taking more than the equivalent of 200 mg of morphine per day. Taking tricyclic antidepressants Questionably valid test performance as indicated by a score of ≤ 85% on the Immediate Recognition, Delayed Recognition or Consistency Scales of the Medical Symptom Validity Test (MSVT) and clinical determination of questionable performance validity by a neuropsychologist on the research team Actively suicidal as evidenced by plan to harm or recent attempt communicated on the Structured Clinical Interview for DSM-V (SCID-5). Increased Intracranial Pressure (ICP) as evidenced through a funduscopic evaluation or on the baseline MRI scan. Moderate or severe cannabis use disorder defined by ≥ 4 symptoms on the SCID-5 Severe alcohol use disorder defined by ≥ 4 symptoms on the SCID-5

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: real APT+ real iTBS<br>real APT+ real iTBS included 30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. iTMS will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (  3 minutes). Participants randomized to active iTBS will receive stimulation at the right dorsolateral prefrontal cortex at 80% active motor threshold . | Device: real iTBS<br>* Intermittent Theta Burst Stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).<br>* Other names: intermittent Theta Burst Stimulation;Behavioral: real APT<br>* APT-III is an attention processing training program<br>* Other names: Attention Processing Training-III;|
| Active Comparator: real APT + placebo iTBS<br>30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. APT-III is a computer based cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation. | Behavioral: real APT<br>* APT-III is an attention processing training program<br>* Other names: Attention Processing Training-III;Device: placebo iTBS<br>* delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).<br>* Other names: sham intermittent Theta Burst Stimulation;|
| Active Comparator: placebo APT+ real iTBS<br>30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Bursts of TMS pulses will be applied at 5Hz rate; each burst consists of 3 pulses delivered at 50Hz rate. The bursts are applied for 2s with 8s inter-burst-intervals, for a total of 600 pulses. The total stimulation time per session is approximately 192s (  3 minutes). Participants randomized to active iTBS will receive stimulation at the right DLPFC at 80% active motor threshold . | Device: real iTBS<br>* Intermittent Theta Burst Stimulation (iTBS) is a form of repetitive transcranial magnetic stimulation (rTMS), which uses short magnetic field pulses applied to the scalp to induce currents in the underlying brain. iTBS will be delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).<br>* Other names: intermittent Theta Burst Stimulation;Behavioral: placebo APT<br>* computerized cognitive training<br>* Other names: Active Control APT;|
| Active Comparator: placebo APT+ placebo iTBS<br>30 1-hour treatment sessions will be provided 3/week. Sessions will be conducted for 10 weeks. Placebo APT-III is a computer based active control cognitive training program. Participants randomized to placebo iTBS will not receive any iTBS stimulation. | Behavioral: placebo APT<br>* computerized cognitive training<br>* Other names: Active Control APT;Device: placebo iTBS<br>* delivered with the Magventure MagProX100 with MagOption stimulator and Magpro Cool Coil B65 A/P. The Magpro Cool Coil B65 A/P can be switched to active or placebo (A/P).<br>* Other names: sham intermittent Theta Burst Stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Mayo Portland Adaptability Inventory (MPAI) | Self-reported ability, adjustment and community participation. It is comprised of 30 items and three subscales: Ability Index, Adjustment Index and Participation Index. Items are scored on a 5-point Likert scale, with lower scores indicating higher levels of functioning. | baseline, 5 weeks, 10 weeks, 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the PTSD Checklist (PCL) | 20-item self-report measure assessing the distress associated with PTSD symptoms. The higher the score, the worse the symptoms. | baseline, 5 weeks, 10 weeks, 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mTBI, PTSD, intermittent theta burst stimulation, cognitive training, neuroimaging