Neuromodulation and Neurorehabilitation for mTBI

Not Applicable

Recruiting

• Conditions: Post Traumatic Stress Disorder; Mild Traumatic Brain Injury
• Interventions: Device: real iTBS; Behavioral: placebo APT; Behavioral: real APT; Device: placebo iTBS

• Registration Number: NCT03819608
• Lead Sponsor: Northwestern University

Brief Summary

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 +/- PTSD.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-15
• Study First Submitted QC: 2019-01-25
• Study First Posted: 2019-01-28
• Study Start: 2021-04-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-04-02
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• At least 18 years of age and no older than 80 years of age
• 3 months post exposure to mTBI event
• Have a history of mTBI with PTSD OR mTBI without PTSD as defined by formalized measures to classify mTBI based on the Symptom Attribution and Classification Algorithm (SACA) and the PTSD Module L of the SCID
• Endorse at least moderate severity on at least one of the four cognitive complaints in the Neurobehavioral Symptom Inventory

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, 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
• Prescribed dosage of mental health medications have been altered within the month preceding study screening. Any participant whose mental health medication(s) has/have changed, within 30 days of study screening. The following are considered a medication change: the addition of or discontinuation of medication, a change in the dose or dosage (daily amount) of medication.
• Taking prescribed CNS stimulants and choosing to not stop these medications during study participation
• 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.
• 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 ≥ 6 symptoms on the SCID-5
• Baseline systolic BP greater or equal to 170

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
real APT+ real iTBS	real iTBS	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 .
placebo APT+ real iTBS	real iTBS	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 .
placebo APT+ placebo iTBS	placebo APT	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.
real APT+ real iTBS	real APT	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 .
real APT + placebo iTBS	placebo iTBS	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.
real APT + placebo iTBS	real APT	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.
placebo APT+ real iTBS	placebo APT	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 .
placebo APT+ placebo iTBS	placebo iTBS	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.

Primary Outcome Measures

Name	Time	Method
Change in the Mayo Portland Adaptability Inventory (MPAI)	baseline, 5 weeks, 10 weeks, 20 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Moody Neurorehabilitation Institute; 🇺🇸 Houston, Texas, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States