A Safety & Efficacy Study With Deep Transcranial Magnetic Stimulation for the Treatment of Post-Traumatic Stress Disorder (PTSD)

A Prospective, Double Blind, Randomized, Controlled Study to Evaluate the Safety and Efficacy of the Brainsway (HAC-Coil) Deep Transcranial Magnetic Stimulation (DTMS) System for the Treatment of Post-Traumatic Stress Disorder (PTSD)

The purpose of the present study is to evaluate the safety and efficacy of Brainsway Deep TMS (DTMS) for the treatment of PTSD.

Study Overview

• Status: Terminated
• Conditions: Post-Traumatic Stress Disorder
• Intervention / Treatment: Device: Sham Treatment; Device: Deep TMS System

Detailed Description

Deep TMS in conjunction with brief trauma exposure will be compared to sham treatment in conjunction with brief trauma exposure, in a multicenter, randomized, controlled study for the treatment of PTSD. Study duration is 9 weeks, consisting of 4 weeks of treatment and a 5 week and 9 week follow-up visit. Subjects will be randomized to real or sham treatment stratified by site. The design is meant to demonstrate that the device shows superiority compared to sham treatment at the 5 week follow-up visit and at the 9 week follow-up visit, 1 month post-treatment.

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Center for Addiction and Mental Health (CAMH)
• Israel
  • Be'er Ya'aqov, Israel, 70350
    • Be'er Yaacov Mental Health Center
  • Tel Hashomer, Israel, 52621
    • Tel Hashomer Hospital
• United States
  • California
    • Los Angeles, California, United States, 90024
      • CalNeuro Research Group
    • Palo Alto, California, United States, CA 94304-1212
      • Stanford University
    • San Diego, California, United States, 92103
      • University Of California - San Diego Medical Center
    • San Diego, California, United States
      • Kadima Neuropsychiatry
  • Florida
    • Gainesville, Florida, United States, 32603
      • University of Florida College of Medicine
    • Juno Beach, Florida, United States, 33408
      • Advanced Mental Health Care Inc. - Juno Beach
    • Palm Beach, Florida, United States, 33411
      • Advanced Mental Health Care Inc.-Palm Beach
    • Royal Palm Beach, Florida, United States, 33411
      • Advanced Mental Health Care Inc. - Royal Palm Beach
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Yellowbrick Foundation
  • New York
    • New York, New York, United States, 11777
      • TMS Hope Center of Long Island
  • North Carolina
    • Raleigh, North Carolina, United States
      • Carolina Partners in Mental Healthcare PLLC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients
• Men and women 22-68 years of age

• Subjects currently diagnosed with PTSD according to the DSM-5, using the CAPS-5 (past-month version), with the following criteria met:

  • Criterion B: at least 1/5 intrusion symptoms; and
  • Criteria C: at least 1/2 avoidance symptoms; and
  • Criteria D: at least 2/7 cognition & mood symptoms; and
  • Criteria E: at least 2/6 arousal & reactivity symptoms; and
  • Criterion F: duration is met; and
  • Criteria G: distress is met.
• Subjects with at least moderate PTSD with a CAPS-5 score ≥ 25 at both Screening and Baseline visits.
• Subjects with an HDRS-21 score ≤ 26 at both Screening and Baseline visits.
• Subjects with negative or mitigated answers on safety screening questionnaire for transcranial magnetic stimulation.
• Negative pregnancy test in childbearing age women.
• Subject is capable and willing to provide informed consent.
• Subject is able to adhere to the treatment schedule.

Exclusion Criteria:

• Subject diagnosed according to the SCID I as suffering from any other major Axis I disorder, such as Psychotic Disorder, Bipolar affective disorder, OCD (MDD is not contraindicated when HDRS-21≤26).
• Subjects diagnosed according to the SCID II as suffering from Severe Personality Disorder.
• Subjects with significant suicidal risk as assessed by the investigator using the Beck Suicide Ideation scale, psychiatric interview or a history of attempted suicide in the past year.
• Subject has a history of epilepsy or seizure (EXCEPT those therapeutically induced by ECT).
• Subject has a history of significant head trauma with loss of consciousness for longer than 5 minutes.
• Subject has a history of cranial surgery.
• Subject has metallic particles in the eye or head (exclusive of mouth), implanted cardiac pacemaker or any intra-cardiac lines, implanted neurostimulators, intra-cranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or implanted medical pumps.
• Subject has severe and frequent headaches.
• Subject has a history of significant hearing loss.

• Subjects with a significant neurological disorder or insult including, but not limited to:

  • Any condition likely to be associated with increased intracranial pressure
  • Space occupying brain lesion
  • History of cerebrovascular accident
  • Transient ischemic attack within two years
  • Cerebral aneurysm
  • MMSE ≤ 24
  • Parkinson's disease
  • Huntington's chorea
  • Multiple sclerosis
• Subject with a history of substance abuse including alcoholism within the past 6 months (except nicotine and caffeine).
• Inadequate communication with the patient.
• Subject is under custodial care.
• Subject is currently participating in another clinical study or enrolled in another clinical study within 30 days prior to this study.
• Subject with unstable physical disease such as unstable cardiac disease.
• Subject is currently on Benzodiazepine at a dose higher than 3 mg of Lorazepam or equivalent.
• Subject has had previous treatment with TMS.
• Women who are breast-feeding.
• Women of childbearing potential and not using a medically accepted form of contraception when sexually active.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Treatment; In the sham treatment,the electrical field induced by the sham coil cannot invoke any action potentials and if no action potentials are induced, then the electric field is insignificant and there is no treatment effect on the brain.	Device: Sham Treatment; Sham treatments will be administered 3 times a week for 4 weeks and additional 2 booster treatments at the 5 and 9 week follow-up visits, for a total of 14 treatment sessions
Experimental: Deep TMS System; Deep Transcranial Magnetic Stimulation (DTMS) is a new form of TMS which allows direct stimulation of deeper neuronal pathways than the standard TMS. The HAC Coil is designed to stimulate neuronal pathways in the medial prefrontal cortex or motor cortex, including the anterior cingulated cortex.	Device: Deep TMS System; Deep TMS treatments will be administered 3 times a week for 4 weeks and additional 2 booster treatments at the 5 and 9 week follow-up visits, for a total of 14 treatment sessions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAPS-5 Score	CAPS-5 Score measured by change from baseline.	5 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Response rate at the 5 week follow-up visit.	5 weeks from baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Measured by vital signs, physical & neurological examinations, lack of significant increase in suicide ideation, & other adverse event reporting.	5 and 9 weeks
Changes in Cognitive Scales	Changes in MMSE and BSRT Scales	5 and 9 weeks

Collaborators and Investigators

• Sponsor: Brainsway
• Investigators: Principal Investigator: Moshe Isserles, MD, Hadassah Ein Karem Medical Center and Center for Addiction and Mental Health (CAMH); Principal Investigator: Zafiris J. Daskalakis, MD, Center for Addiction and Mental Health (CAMH); Principal Investigator: Avraham Zangen, PhD, Ben-Gurion University of the Negev

Publications and helpful links

General Publications

• Isserles M, Tendler A, Roth Y, Bystritsky A, Blumberger DM, Ward H, Feifel D, Viner L, Duffy W, Zohar J, Keller CJ, Bhati MT, Etkin A, George MS, Filipcic I, Lapidus K, Casuto L, Vaishnavi S, Stein A, Deutsch L, Deutsch F, Morales O, Daskalakis ZJ, Zangen A, Ressler KJ. Deep Transcranial Magnetic Stimulation Combined With Brief Exposure for Posttraumatic Stress Disorder: A Prospective Multisite Randomized Trial. Biol Psychiatry. 2021 Nov 15;90(10):721-728. doi: 10.1016/j.biopsych.2021.04.019. Epub 2021 May 4.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2016
• Primary Completion (Actual): February 6, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: June 23, 2015
• First Posted (Estimate): June 24, 2015

Study Record Updates

• Last Update Posted (Actual): May 14, 2020
• Last Update Submitted That Met QC Criteria: May 13, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: PTSD; Post-Traumatic Stress Disorder; dTMS
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: CTP-PTSD-01