Novel Treatment of Emotional Dysfunction in Post Traumatic Stress Disorder (PTSD)

Not Applicable

Completed

Conditions: Post Traumatic Stress Disorder

Interventions: Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Device: Repetitive Transcranial Magnet Stimulation (rTMS)
Behavioral: Cognitive Processing Therapy

Registration Number: NCT01391832

Lead Sponsor: The University of Texas at Dallas

Brief Summary: The objective will be to determine if adding repetitive transcranial magnetic stimulation prior to Cognitive Processing Therapy significantly enhances recovery from hyperarousal symptoms in individuals with combat related post traumatic stress disorder and improves clinical outcome.

The investigators have assembled a multimodal human performance laboratory including 64 channel EEG and repetitive transcranial magnetic stimulation system. These resources combined with the neuroimaging capabilities of the Advanced Imaging Research Center (AIRC) at UT Southwestern and skilled Cognitive Processing Therapy (CPT) practitioners will be used in this study.

The study involves approximately 19 visits. Treatment is once a week for 12 weeks followed by a 1 month, 3 month and 6 month follow-up appointments.

Detailed Description: We will first screen participants between the ages of 18 and 60 years for symptoms of PTSD as determined by subjective reporting. We will also screen for healthy control participants to participate in comparison assessment phases of the study. After meeting pre-screen criteria, a more extensive screening to determine the eligibility of each subject will be performed. This will be followed by an EEG. The EEG system measures event-related potentials (ERPs), which explain certain cognitive processes based on changes in the amplitude and timing of electrical changes recorded from the surface of the scalp. We will use an ERP task that includes combat-threatening stimuli as the novel oddball probe to assess P300 response. The amplitude of the P300 (positive amplitude recorded 300 milliseconds after stimulus onset) is used to differentiate between hypo-, normo-, and hyper-arousability. Identifying those with hyperarousal on P300 response on ERP allows for identification of PTSD patients with subjective and objective measures of hyperarousal. The participants will then be scheduled for a neuroimaging session. During neuroimaging, participants will have structural and functional brain scans acquired, including a functional MRI scan using the same threatening/nonthreatening stimuli, thus providing another objective measure of hyperarousal.

Participants will then have active or sham 1 Hz repetitive transcranial magnetic stimulation (rTMS) administered to the right frontal lobe as well as Cognitive Processing Therapy (CPT) once per week for twelve weeks (total 12 rTMS-CPT sessions). Studies have shown that rTMS applied externally to the forehead in the region of the dorsal lateral forehead will safely, reversibly, and painlessly down-modulate the frontal lobe on the side of the head to which it is applied. Our preliminary studies have shown that application of frontal rTMS can reduce the response to threatening stimuli temporarily and this can optimize the effectiveness of the CPT. Following the 12 sessions of rTMS-CPT, the EEG and neuroimaging will be repeated to test for changes in brain function.

In summary, the study involves approximately 19 visits. Treatment is once a week for 12 weeks followed by a 1 month, 3 month and 6 month follow-up appointments.

* The first 2-3 visits involve an informed consent, a baseline assessment, EEG and neuroimaging.

* Visits 4-15 are the rTMS/CPT sessions.

* Visit 16 is a 1 month follow-up, post-treatment assessment and EEG.

* Visit 17 is a post-treatment neuroimaging visit.

* Visit 18 is the 3 month follow up assessment.

* Visit 19 is the 6 month follow-up assessment.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 103

Inclusion Criteria

Veterans of Operation Iraqi Freedom (OIF) or Operation Enduring Freedom (OEF)
18-60 years
Diagnosis or symptoms of Combat related PTSD/ PCL Score Indicative of diagnosis (prior diagnosis not required).
English speaking
Participants will be screened for exclusionary medical and mental health history.

This study is also looking for civilian and miltary control subjects for assessment phase participation.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
active rTMS	Repetitive Transcranial Magnet Stimulation (rTMS)	Active Repetitive Transcranial Magnet Stimulation treatment Intervention: Device: Active rTMS of dorsolateral pre-frontal cortex
Sham rTMS	Cognitive Processing Therapy	Sham Treatment Intervention: Device: Repetitive Transcranial Magnet Stimulation (sham treatment)
active rTMS	Cognitive Processing Therapy	Active Repetitive Transcranial Magnet Stimulation treatment Intervention: Device: Active rTMS of dorsolateral pre-frontal cortex
Sham rTMS	Repetitive Transcranial Magnetic Stimulation (rTMS)	Sham Treatment Intervention: Device: Repetitive Transcranial Magnet Stimulation (sham treatment)

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Follow-up in Clinician Administered Post-Traumatic Stress Disorder Scale Total Severity Score	Outcome measures will be measured as change from baseline at 1-, 3-, and 6-month follow-ups	The primary outcome measure of treatment efficacy for post-traumatic stress disorder (PTSD) will be change in the Clinician Administered Post-Traumatic Stress Disorder Scale (CAPS) Total Severity Score (i.e., summed across frequency and intensity ratings for the 17 PTSD assessment items) from baseline at 1-month post-treatment. CAPS Total Severity Score ranges from 0 to 136. Difference scores were calculated as the outcome score minus the baseline score, with negative scores indicating a reduction in symptom severity from baseline (i.e., a positive treatment outcome), and differences between treatment groups in change scores were evaluated using t-tests.

Secondary Outcome Measures

Name	Time	Method
Changes in ERP/CAPS Cluster Scores Signals From Pre-Treatment to Post-Treatment	Outcomes will be assessed at baseline and 6-month follow-up	The secondary outcome measures will be a) the ERP measures of P3a amplitude for hyperarousal to combat threatening stimuli will be compared from post- to pre-treatment b) the total CAPS scores from pre-treatment and post-treatment will be compared.