Neuromodulation and Neurorehabilitation for mTBI

Northwestern University

Status: Enrolling

Conditions: Post Traumatic Stress Disorder; Mild Traumatic Brain Injury

Treatments: Behavioral: real APT; Behavioral: placebo APT; Device: real iTBS; Device: placebo iTBS

Study type: Interventional

Funder types: Other

Identifiers

NCT03819608

1034818

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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200 participants in 4 patient groups

real APT+ real iTBS

Experimental group

Description:

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 .

Treatment:

Device: real iTBS

Behavioral: real APT

real APT + placebo iTBS

Active Comparator group

Description:

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.

Treatment:

Device: placebo iTBS

Behavioral: real APT

placebo APT+ real iTBS

Active Comparator group

Description:

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 .

Treatment:

Device: real iTBS

Behavioral: placebo APT

placebo APT+ placebo iTBS

Active Comparator group

Description:

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.

Treatment:

Device: placebo iTBS

Behavioral: placebo APT