rTMS for PTSD Comorbid With Major Depressive Disorder

• ClinicalTrials.gov Identifier: NCT02273063
• Recruitment Status: Completed
• First Posted: October 23, 2014
• Results First Posted: October 4, 2018
• Last Update Posted: October 4, 2018
• Sponsor: Butler Hospital
• Collaborators: Providence VA Medical Center; Neuronetics
• Information provided by (Responsible Party): Butler Hospital

Tracking Information

• First Submitted Date: October 15, 2014
• First Posted Date: October 23, 2014
• Results First Submitted Date: May 9, 2018
• Results First Posted Date: October 4, 2018
• Last Update Posted Date: October 4, 2018
• Study Start Date: October 2014
• Actual Primary Completion Date: April 22, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2018)

• Total Score on PTSD Checklist for DSM-5 (PCL-5) [ Time Frame: Baseline to final TMS session (up to 40 sessions over up to 8 weeks) ]
  This self-report scale is called: "PTSD Checklist for DSM-5" (abbreviated PCL-5) (see https://www.ptsd.va.gov/professional/assessment/adult-sr/ptsd-checklist.asp). Total PCL-5 score ranges from 0 to 80. Analysis of treatment effect on symptom severity will be evaluated by change in PCL-5 total score from baseline (pre-TMS) to endpoint (post-TMS)(or LOCF); Paired t-test compares the mean total PCL-score for the group at the two time points. A higher total score on the PCL-5 scale corresponds with more severe PTSD symptoms than a lower total score. A greater change from baseline to endpoint would correspond with better treatment outcome.
• Total Score on Inventory of Depressive Symptomatology, Self-Report (IDS-SR) Scale [ Time Frame: Baseline to final TMS session (up to 40 sessions over up to 8 weeks) ]
  This self-report scale is called "Inventory of Depressive Symptomatology, Self-Report" (Abbreviated IDS-SR). IDS-SR Total Scores Range from 0 to 84, with a higher score reflecting greater depressive symptom severity. Paired t-test compares the change in mean total IDS-SR score from baseline (pre-TMS) to endpoint (last TMS session) or LOCF. A greater change reflects a better outcome than lesser change.

Original Primary Outcome Measures (submitted: October 21, 2014)

• Efficacy of 5 Hz rTMS on self-reported PTSD symptoms [ Time Frame: Up to 15 months ]
  Improvement in self-rated scales for PTSD (e.g., PTSD checklist [PCL])
• Efficacy of 5 Hz rTMS on self-reported MDD symptoms [ Time Frame: Up to 15 months ]
  Improvement in self-rated scales for MDD (e.g., Inventory of Depressive Symptoms Self-Report [IDSSR], PHQ-9)

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: October 21, 2014)

• Improvements in Quality of life associated with 5 Hz rTMS [ Time Frame: Up to 15 months ]
  Improvements in self-rated quality of life (e.g., quality of life questionnaire [Q-LES-Q])
• Improvements in patient and clinician rated global impression [ Time Frame: Up to 15 months ]
  Improvements in global clinical status (e.g., CGI-S)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: rTMS for PTSD Comorbid With Major Depressive Disorder
• Official Title: 5Hz Repetitive Transcranial Magnetic Stimulation for Posttraumatic Stress Disorder Comorbid With Major Depressive Disorder
• Brief Summary: The purpose of this study is to see how well a treatment called "Repetitive Transcranial Magnetic Stimulation" works for patients who struggle with symptoms of both posttraumatic stress disorder and major depressive disorder.
• Detailed Description: This study aims to evaluate the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for adults with comorbid posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Although standard rTMS uses stimulations delivered to the left prefrontal cortex at 10 pulses per second, prior work has shown that other stimulation frequencies may work for both PTSD and MDD. In this study, we examine the efficacy of left-sided 5Hz in patients with PTSD and MDD, hypothesizing that this lower frequency will improve PTSD and MDD symptoms.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Posttraumatic Stress Disorder
• Major Depressive Disorder
• Transcranial Magnetic Stimulation, Repetitive

Intervention

Device: Transcranial Magnetic Stimulation (TMS)

Up to 40 sessions of TMS delivered with the first 35 sessions delivered over 7 weeks, and final 5 treatments delivered in taper schedule over 3 weeks. Treatment is adjunct to ongoing stable pharmacotherapy.

Other Name: Neuronetics' NeuroStar TMS Therapy System

Study Arms

Experimental: Transcranial Magnetic Stimulation

Stimulation at pulse frequency of 5Hz delivered over L DLPFC. Intensity: 120% of Motor Threshold, 5 Sec Train, 14 Sec Inter-Train Interval, Frequency: 5Hz, Total Pulses: 3000/session. Sessions delivered once/day on weekdays for up to 40 sessions.

Intervention: Device: Transcranial Magnetic Stimulation (TMS)

Publications *

• Carpenter LL, Conelea C, Tyrka AR, Welch ES, Greenberg BD, Price LH, Niedzwiecki M, Yip AG, Barnes J, Philip NS. 5 Hz Repetitive transcranial magnetic stimulation for posttraumatic stress disorder comorbid with major depressive disorder. J Affect Disord. 2018 Aug 1;235:414-420. doi: 10.1016/j.jad.2018.04.009. Epub 2018 Apr 5.
• Philip NS, Barredo J, van 't Wout-Frank M, Tyrka AR, Price LH, Carpenter LL. Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Biol Psychiatry. 2018 Feb 1;83(3):263-272. doi: 10.1016/j.biopsych.2017.07.021. Epub 2017 Aug 8.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 21, 2014): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 22, 2016
• Actual Primary Completion Date: April 22, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. To ensure subjects can safely receive rTMS, eligible subjects must meet all established screening criteria for safety during MRI (magnetic resonance imaging), since MRI involves magnetic fields at similar intensity to those emitted from the rTMS treatment coil. These are conservative measures require a patient not having the following (unless MRI-safe): Cardiac pacemaker, implanted device (deep brain stimulation) or metal in the brain, cervical spinal cord, or upper thoracic spinal cord;
2. Outpatients 18-70 years of age (inclusive)
3. Meet DSM-IV criteria for MDD (recurrent or single episode chronic) and PTSD (acute or chronic) at the time of the screening and baseline visits;
4. Have a baseline score of "Moderately Ill" or worse on both the CGI-S and the PGI-S.
5. Have failed at least one antidepressant medication trial as part of definitive and adequate treatment in the current episode, OR have demonstrated intolerance to at least one antidepressant medication as part of attempted treatment in the current episode of illness (i.e., meet FDA labeling requirements for administration of rTMS for depression);
6. Be on a stable psychotropic regimen for at least six weeks (42 days) prior to screening, or no psychotropic medication at all, and be willing to maintain the current regimen and dosing for the duration of the study (unless medical necessary to make changes with notification of research staff);
7. If female and of child bearing potential, agree to use an acceptable method of birth control for the duration of the study treatment period
8. Be willing and able to comply with all study related procedures and visits,
9. Be capable of independently reading and understanding patient information materials and giving written informed consent.

Exclusion Criteria:

1. Are pregnant or lactating or planning to become pregnant within the next three months.
2. Have a lifetime history of loss of consciousness due to head injury for greater than 10 minutes, or any lifetime history of loss of consciousness due to a head injury with documented evidence of brain injury (including brain atrophy).
3. Current (or past if appropriate) significant neurological disorder, or lifetime history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d) cerebral aneurysm;
4. Current Axis 1 primary psychotic disorder, or bipolar I disorder, current alcohol and/or substance dependence or abuse within the past 1 month;
5. Past treatment with TMS therapy
6. Have active suicidal intent or plan as detected on screening assessments, or in the Investigator's opinion, is likely to attempt suicide within the next six months.
7. Demonstrate the presence of any other condition or circumstance that, in the opinion of the investigator, has the potential to prevent study completion and/or to have a confounding effect on outcome assessments.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02273063
• Other Study ID Numbers: 1404-005
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Butler Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Butler Hospital
• Original Study Sponsor: Same as current

Collaborators

• Providence VA Medical Center
• Neuronetics

Investigators

• Principal Investigator: Linda L Carpenter, M.D.; Butler Hospital

• PRS Account: Butler Hospital
• Verification Date: October 2018