Novel Treatment of Emotional Dysfunction in Post Traumatic Stress Disorder (PTSD)
Condition: Post Traumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

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.
    

Intervention name(s): Repetitive Transcranial Magnetic Stimulation (rTMS); Cognitive Processing Therapy; Repetitive Transcranial Magnet Stimulation (rTMS)
Intervention type(s): Device; Behavioral; Device
Intervention description(s): For the sham rTMS with CPT group, the rTMS coil will be placed over the right prefrontal scalp region with the MagStim Rapid Stimulator set to the sham mode so that all conditions are similar to the active delivery mode except that transcranial magnetic stimulation is not administered to the scalp and does not down modulate the right frontal lobe.; Cognitive Processing Therapy (CPT) is a 12 session evidenced based, trauma-focused treatment for PTSD. CPT is a cognitive therapy based on information processing theory and includes components which help the client to (a) access her or his memory of the event, (b) identify and experience her or his emotions until they have been extinguished, and (c) identify and challenge beliefs about the event itself and beliefs about self and the world which have been altered because of the combat related trauma.; For the active rTMS with CPT group, the rTMS coil will be placed over the right prefrontal scalp region with the MagStim Rapid Stimulator set to the active mode. After motor threshold determination, the stimulator coil is positioned over the dorsolateral prefrontal cortex - DLPFC (Brodmann Area 9/46). The right frontal rTMS will safely, reversibly, and temporarily down modulate the right frontal lobe. The conducting coil is placed over the scalp while electrical current pulses pass through the coil. This alternating current turned on and off rapidly produces magnetic pulses (1.5-2.0 Tesla strength) that last for 100 - 300 microseconds. The time-varying magnetic pulses induce an electrical field that will result in current flow in neural tissue, thereby activating or deactivating cortex subjacent to the coil.
Other intervention name(s): rTMS; magnet stimulation; CPT; behavioral training; behavioral therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
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