Study Testing if Fast or Slow rTMS is Better for the Treatment of Posttraumatic Stress Disorder (PTSD)
Condition: Posttraumatic Stress Disorder; Depression
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      Objectives: The primary objective is to test whether right prefrontal cortex low frequency 1
      Hz rTMS versus right prefrontal high frequency 10 Hz rTMS provides a significantly greater
      improvement in function as measured by IPF score and PTSD symptoms as measured with CAPS
      score. The secondary objectives include: one, testing which treatment provides a
      significantly greater improvement in depressive symptoms as measured by change in QIDS score;
      two, testing whether depression impacts effectiveness of 1 Hz versus 10 Hz rTMS for PTSD
      symptoms; three, testing which treatment is better tolerated as measured by participant drop
      out and side effect profiles.

      Research Design: Randomized single-blind (raters) prospective clinical trial testing the
      effectiveness 1 Hz rTMS versus 10 Hz rTMS in veterans with PTSD.

      Methodology: Veterans 18-50 years of age suffering from PTSD with and without depressive
      symptoms will be recruited from the community as well as mental health clinics at James A.
      Haley Veterans Administration Hospital. Plan to enroll 50 to have an evaluable sample of
      approximately 20 in each group. Participants will be consented and undergo screening for
      safety and appropriateness to be in the trial. Those deemed eligible will be evaluated with
      clinical measures of function, PTSD, depression, pain, and neurobehavioral symptoms.
      Participants will be randomized in equal proportion (stratified by significant depression
      defined as MADRS greater than 19) to one of two active treatments: right prefrontal 1 Hz rTMS
      versus right prefrontal 10 Hz rTMS. Participants will undergo assessment for safety prior to
      each treatment. The treatments will be performed 5 days a week for 6 weeks with a 3-week
      taper consisting of 3 days per week, 2 days per week, and 1 day per week. Clinical
      evaluations will be performed at baseline, after every five treatments, at the end of
      treatment, and at 1 and 3 months post treatment. CAPS and IPF scores will be used to
      determine if there is a significant difference between 1 Hz and 10 Hz right prefrontal rTMS
      for PTSD symptoms and function respectively. The QIDS scores will be used to test for a
      significant difference in change in depressive symptoms for both the participants with
      significant depressive symptoms and the entire group. The number of dropouts (related
      specifically to side effects and all cause) will be used along with side effect profiles to
      test for differences in tolerability of the two treatments.
    

Detailed description: 
      Participants wishing to participate will contact the study team either personally or through
      their provider at the Veteran's request. Further means of recruitment are as follows. 1)
      Flyers will be placed at the University of South Florida and other high learning institutions
      in the local area. 2)The study team will provide flyers and give talks at Veteran associated
      organizations. 3)The study will also be advertised on the JAH Facebook page as well as the
      JAH Twitter account. 4) Veterans with a PTSD diagnosis will be identified using the VSSC web
      reports. Using this method, the study staff will pre-screen the CPRS records of 5,000
      veterans to identify potential subjects. The identified veterans will be sent a recruitment
      letter with detailed information about the study as well as a copy of the informed consent.
      After a 10-day waiting period, the study team will them contact the veteran by phone to see
      if they are interested in participating. The study team will review the Veteran's medical
      record and discuss the study and its entry criteria with the participants and/or provider.
      Those suitable to enter the trial and interested will be scheduled for a screening/baseline
      visit. These participants will typically be those who have either failed or are not willing
      to engage in standard evidence-based psychotherapy.

      The screening/baseline visit will begin by acquiring written informed consent. Subsequently,
      evaluations to determine safety and appropriateness, as well as clinical ratings and
      laboratory testing (UDS and urine pregnancy testing) will be performed. Those deemed eligible
      will be randomized to 1 Hz versus 10 Hz stratified by significant depression (MADRS > 19) and
      treated on a subsequent day within a week. Participants will be treated for 5 days a week for
      6 weeks with a 3-week taper (3 per week for 1 week, 2 per week for 1 week, 1 per week for 1
      week). Participants will undergo clinical evaluation weekly for clinical effect during the
      treatment, at the end of the taper (or when participant chooses to leave the trial) and at 1-
      and 3-months post treatment. In addition, safety will be assessed prior to each treatment.
      The total time in study for a participant will be approximately 22 weeks.

      Randomization will be stratified based on significant depressive symptoms which will be
      defined as a MADRS score > 19 versus MADRS score ≤ 19. Using a computer randomization
      schedule, an investigator not involved directly with the trial will generate two random lists
      of active and sham cards that will be placed in envelopes. The two groups will be MADRS score
      > 19 versus MADRS score ≤ 19. When the participant is ready to begin the first treatment, the
      treater will pull the next envelope in line for the appropriate group and open the envelope
      to determine the randomization assignment. The participant will know the assignment as well
      as the treater but the investigator doing all the clinician rating scales will be masked to
      assignment.

      Medications and other treatments: Participants will be allowed to continue current
      medications and therapy as long as does not increase risk of rTMS and is held constant during
      the six weeks of the trial. Doses may be adjusted as need for side effects.

      Materials obtained for research purposes include demographic information, contact information
      (for purposes of the study only), medical/psychiatric history (from interviews/
      questionnaires), cognitive test data, laboratory data, and clinical data. All of the data
      will be obtained for research purposes.

      Treatment with the Neurostar (Repetitive Transcranial Magnetic Stimulation) Stimulation
      System may involve other risks that are not known at the present time. The long-term effects
      of rTMS (Repetitive Transcranial Magnetic Stimulation) are not known. Legal and social risks
      of participation in this research are unknown.

      The PI will monitor the safety of the participants to continue in the trial. The PI will be
      seeing the participants in person typically on at least a weekly basis. The PI will review
      the study data for side effects on an ongoing basis but more formally every 12 months to
      ensure no trends in the data of increased risk.

      The data will only be used by the research team within the VA to address the research
      questions.
    

Intervention name(s): Repetitive Transcranial Magnetic Stimulation
Intervention type(s): Device
Intervention description(s): TMS Device
Other intervention name(s): NeuroStar chair (Neuronetics, Malvern, PA)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Transcranial Magnetic Stimulation; TMS; PTSD