An Evaluation of the Safety and Efficacy of the dTMS Treatment for OCD

A Prospective Double Blind Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Deep Transcranial Magnetic Stimulation (dTMS) in Obsessive-Compulsive Subjects

The purpose of the study is to evaluate the safety and efficacy of the Deep TMS (DTMS) treatment in subjects with OCD. The device technology is based on the application of deep brain TMS by means of repetitive pulse trains at a predetermined frequency. The Brainsway DTMS study is a randomized, 10 week, double blind, multi-center trial comparing active DTMS treatment to sham treatment.

Study Overview

• Status: Completed
• Conditions: Obsessive Compulsive Disorder
• Intervention / Treatment: Device: Active DTMS Treatment; Device: Sham Treatment

Detailed Description

The OCD study will compare one group of OCD subjects receiving DTMS treatment (HAC-coil) to a second group of OCD subjects receiving sham treatment (sham coil). The treatment group will receive 5 weeks of daily DTMS treatments followed by 4 treatments in week 6, for a total of 29 treatment sessions. The control group will receive the same treatments with a sham coil. Subjects may continue to take SSRI medications (if prescribed) and any other antidepressant medications will be tapered down prior to the first treatment. SSRI medications approved for OCD include Fluoxetine (Prozac, Sarafem, Symbyax), Fluvoxamine (Luvox, Luvox CR), Paroxetine (Paxil, Paxil CR, Pexeva) and Sertraline (Zoloft). Efficacy will be assessed using the Yale-Brown Obsessive Compulsive Scale score (YBOCS), as well as other efficacy scales. Safety will be assessed by monitoring of adverse events, vital signs, physical and neurological examination and using certain safety questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Center for Addiction and Mental Health (CAMH)
• Israel
  • Tel Hashomer, Israel, 52621
    • Tel Hashomer Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California (UCLA)
    • San Diego, California, United States, 92093
      • University of California
  • 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
    • Royal Palm Beach, Florida, United States, 33411
      • Advanced Mental Health Care Inc. - Royal Palm Beach
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 11777
      • TMS Hope Center of Long Island
    • New York, New York, United States, 10021
      • Neuropharmacology Services
  • Ohio
    • Mason, Ohio, United States, 45040
      • Lindner Center of HOPE, University of Cincinnati College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 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 diagnosed as suffering from OCD according to the DSM-IV-TR.
• Subjects with at least moderate OCD, rating a YBOCS score of >20.
• Subjects are maintained on SSRI medication at at least a therapeutic dosage for at least 2 months prior to study entry and for the duration of the trial and/or subjects are maintained on psychotherapeutic behavioral intervention therapy (subjects undergoing CBT treatment must be in the maintenance stage (i.e., not during the assessment or skills acquisition or training stages).
• Subjects with negative responses on the Transcranial Magnetic Stimulation Safety Screening questionnaire (TASS).
• According to the treating physician the subject is compliant with taking medication, if applicable.
• Subject is capable and willing to provide informed consent.
• Subject is able to adhere to the treatment schedule.

Exclusion Criteria:

- • Subjects diagnosed according to the SCID I as suffering from any other Axis I diagnosis as the primary diagnosis.

• Subjects diagnosed according to the SCID II as suffering from severe Personality Disorder (excluding Obsessive Compulsive Personality Disorder) or hospitalized due to exacerbation related to borderline personality disorder.
• Present suicidal risk as assessed by the investigator using the Scale for Suicide Ideation (SSI), brief mental status exam and psychiatric interview or significant suicide risk based on HDRS-21 item 3 score of 3 or 4 or a history of attempted suicide in the past year.
• Subject has a history of epilepsy or seizure (EXCEPT those therapeutically induced by ECT) or history of such in first degree relatives.
• Subject has an increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure, or history of significant head trauma with loss of consciousness for greater than or equal to 5 minutes.
• Subject has a history of head injury necessitating cranial surgery or prolonged coma.
• Subject has a history of any metal in the head including the eyes and ears (outside the mouth).
• Subject has known history of any metallic particles in the eye, implanted cardiac pacemaker or any intracardiac lines, implanted neurostimulators, intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or implanted medical pumps.
• Subject has a history of significant hearing loss.
• Subjects with significant neurological disorder or insult including, but not limited to:
• Any condition likely to be associated with increased intracranial pressure
• Subject has a history of substance abuse including alcoholism within the past 6 months (except nicotine and caffeine).
• Inadequate communication with the patient.
• Subject is currently participating in another clinical study or enrolled in another clinical study within 30 days prior to this study.
• Subjects who suffer from an unstable physical, systemic and metabolic disorder such as unstabilized blood pressure or acute, unstable cardiac disease.
• Subject is currently on any antidepressant medication other than SSRIs.
• Subject is currently on Clomipramine
• Subject has had previous treatment with TMS
• Women who are breast-feeding
• Women who are pregnant or with suspected pregnancy
• Women of childbearing potential and not using a medically accepted form of contraception when engaging in sexual intercourse.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active DTMS Treatment; Active DTMS Treatment constitutes the Deep Transcranial Magnetci Stimulation (DTMS) which is a new form of TMS which allows direct stimulation of deeper neruonal pathways than the standard TMS. The DTMS coil is designed to allow deeper brain stimulation without significant increase of electric fields included in superficial cortical regions.	Device: Active DTMS Treatment; H-coil Deep TMS 29 TMS treatments over 6 weeks.
Sham Comparator: Sham Treatment; The Sham Treatment consists of an electrical field which 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; 29 treatments over 6 weeks.; Other Names: Deep TMS Sham treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale Brown Obsessive Compulsive Scale (YBOCS) score	The primary objective of the study is to compare the change in Yale Brown Obsessive Compulsive Scale (YBOCS) scores from baseline to the 6 week (post-randomization) visit, between the two treatments groups.	6 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale Brown Obsessive Compulsive Scale (YBOCS), Sheehan Disability Scale (SDS), Clinical Global Impression - Severity Scale (CGI-S), Clinical Global Impression - Improvement Scale (CGI-I)	The secondary effectiveness objectives of the study are: i. Change from baseline to 6 weeks in Yale Brown Obsessive Compulsive Scale (YBOCS) (and other assessment scale) scores, between treatment groups. ii. Response rate at 6 weeks in Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline, between treatment groups; iii.Partial Response rate at 6 weeks in Yale Brown Obsessive Compulsive Scale (YBOCS) score, between treatment groups; iv. Change from baseline to 10 weeks in above scales. v. Remission rates at 6 weeks between treatment groups.	6 Weeks and 10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events, changes in vitals signs, physical and neurological results, changes in suicide scale and changes in cognitive scales	Safety of the DTMS treatment as defined by maintained subject baseline, pre-treatment, physical and neurological examinations and lack of significant increase in suicide ideation measured by: Vital signs; Physical and neurological examination; Scale for Suicide Ideation; Cognitive evaluation using the Mini-Mental State Exam (MMSE), Buschke Selective Reminding Test (BSRT) and Autobiographical Memory Interview - Short Form (AMI-S) scales; Any other adverse events (AEs).	10 Weeks

Collaborators and Investigators

• Sponsor: Brainsway
• Investigators: Principal Investigator: Joseph Zohar, Prof, Tel Hashomer Hospital; Principal Investigator: Abraham Zangen, Prof, Soroka University Medical Center

Publications and helpful links

General Publications

• Harmelech T, Tendler A, Roth Y, Zangen A. Do comorbid OCD-MDD patients need two separate dTMS protocols? Brain Stimul. 2020 Jul-Aug;13(4):1000-1001. doi: 10.1016/j.brs.2020.03.014. Epub 2020 Mar 31. No abstract available.
• Crowell AL, Riva-Posse P, Holtzheimer PE, Garlow SJ, Kelley ME, Gross RE, Denison L, Quinn S, Mayberg HS. Long-Term Outcomes of Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression. Am J Psychiatry. 2019 Nov 1;176(11):949-956. doi: 10.1176/appi.ajp.2019.18121427. Epub 2019 Oct 4.
• Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1;176(11):931-938. doi: 10.1176/appi.ajp.2019.18101180. Epub 2019 May 21.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: August 7, 2014
• First Submitted That Met QC Criteria: August 28, 2014
• First Posted (Estimate): September 3, 2014

Study Record Updates

• Last Update Posted (Actual): July 15, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: OCD
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Obsessive-Compulsive Disorder
• Other Study ID Numbers: CTP-OCD-01