Clinical trial NCT01391832: Novel Treatment of Emotional Dysfunction in Post Traumatic Stress Disorder (PTSD)
Official title: Novel Treatment of Emotional Dysfunction in PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post Traumatic Stress Disorder
Keywords: rTMS
PTSD
Post Traumatic Stress Disorder
repetitive transcranial magnetic stimulation
combat related PTSD
OEF
OIF
Veterans
operation enduring freedom
operation iraqi freedom
CPT
cognitive processing therapy
Lead sponsor: The University of Texas at Dallas
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: University of Texas Southwestern Medical Center
First posted: 2011-07-12
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline to Follow-up in Clinician Administered Post-Traumatic Stress Disorder Scale Total Severity Score
timeFrame: Outcome measures will be measured as change from baseline at 1-, 3-, and 6-month follow-ups
Secondary outcomes:
measure: Changes in ERP/CAPS Cluster Scores Signals From Pre-Treatment to Post-Treatment
timeFrame: Outcomes will be assessed at baseline and 6-month follow-up
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas at Dallas
state: Texas
Study officials:
affiliation: University of Texas at Dallas
name: John Hart Jr., M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas
name: F. Andrew Kozel, M.D.
role: STUDY_DIRECTOR
References: