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Transcranial Magnetic Stimulation (TMS) and Obsessive Compulsive Disorder (OCD)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00106249
First Posted: March 22, 2005
Last Update Posted: January 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
New York State Psychiatric Institute
  Purpose

This study will evaluate the clinical efficacy of functional Magnetic Resonance Imaging (fMRI) guided 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) applied to the Supplementary Motor Area (SMA) in OCD patients who have not fully responded to conventional therapies. The investigators will collect TMS measures of motor cortex excitability to test whether rTMS restores normal levels of intracortical inhibition found to be deficient in OCD. The investigators hypothesize that:

  1. Compared to sham (placebo), active rTMS will improve symptoms of OCD as assessed with the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression (CGI).
  2. Active (but not sham) rTMS will normalize levels of motor cortex excitability, as reflected by increased intracortical inhibition, motor threshold, and cortical silent period, and by decreased intracortical facilitation, relative to pre-treatment baseline.

Condition Intervention Phase
Obsessive-Compulsive Disorder Device: Repetitive Transcranial Magnetic Stimulation (rTMS) Device: Sham Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Obsessive Compulsive Disorder (OCD) With Transcranial Magnetic Stimulation (TMS)

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Clinical Improvement (Yale-Brown Obsessive Compulsive Scale/Y-BOCS) [ Time Frame: Through study completion ]
    Response rate was defined as a decrease >25% on the YBOCS-SR. Y-BOCS-Self Report (Baer et al. 1993) is very similar to the clinician-administered one, and has shown excellent internal consistency and test-retest reliability, performing somewhat better than the interview (Steketee et al., 1996); subjects are asked to focus on the main obsessions and main compulsions and to answer five questions: time spent, interference, distress, resistance, and control. Consistent with the interview format, subjects rate each item on a 0 (none) to 4 (extreme) scale.


Secondary Outcome Measures:
  • Motor Cortex Excitability (Motor Threshold) [ Time Frame: Through study completion ]
    In 22 OCD patients, who completed the RCT, we applied the new customized software for acquisition and analysis of neurophysiology data that was developed to allow for automatic control of the TMS devices during motor cortex excitability measures. Specifically, the software delivers TMS pulses and automatically determines motor threshold (MT); a descending staircase method is utilized, starting at the intensity at which the optimal site selection for the MT is determined. After each stimulus in the MT experiments, the software would prompt the user to confirm the automated MEP-detection.

  • Motor Cortex Excitability (Short Intracortical Inhibition) [ Time Frame: Through study completion ]
    In 22 OCD patients enrolled in the RCT, we applied the new customized software for acquisition and analysis of neurophysiology data that was developed to allow for automatic control of the TMS devices during motor cortex excitability measures. For the paired-pulse (PP) measurements of short intracortical inhibition (SICI) the interstimulus interval (ISI) was set to 8-12 seconds on a continuous uniform distribution. The FPGA board samples the EMG data, controls the timing of the TMS stimuli, and also controls the intensity of the devices.


Enrollment: 27
Study Start Date: November 2004
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active rTMS
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
Stimulus train of 30 min duration, 1Hz frequency, and 110% of the motor threshold intensity given once a day, 5 days a week, for 4 weeks by Magstim SuperRapid Magnetic Stimulator.
Other Name: Magstim Rapid2, Magstim SuperRapid, Magstim Rapid, Magstim
Sham Comparator: Sham rTMS
Placebo Repetitive Transcranial Magnetic Stimulation (rTMS)
Device: Sham
Sham rTMS will be administered using the Magstim Sham coil which contains a mu-metal shield that diverts the majority of the magnetic flux such that a minimal (less than 3%) magnetic field is delivered to the cortex in order to provoke a subjective sensation similar to that obtained with the real stimulation but without inducing significant cortical stimulation.

Detailed Description:

This study tests the efficacy of functional Magnetic Resonance Imaging (fMRI) guided repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Obsessive Compulsive Disorder (OCD). This study also examines measures of brain function that may inform us about the brain basis underlying OCD.

Despite major advances in the study and treatment of OCD, patients often do not respond or experience only partial remission from pharmacotherapy or cognitive behavioral therapy. rTMS is a non-invasive procedure that allows stimulation of the brain using magnetic fields. Some studies have reported that rTMS may be helpful in reducing obsessive and compulsive symptoms. While promising, prior research has several limitations (e.g., relatively small sample sizes, stimulation of sub-optimal target areas, relatively short durations of treatment, and lack of sham (placebo) comparison).

This study addresses the drawbacks of prior work, and will provide data that will be important in determining whether rTMS can be useful for OCD patients resistant to conventional therapies. In this trial, 32 adult outpatients with OCD, that have been only partially responsive to conventional therapies, will be randomly assigned to one of two treatment groups (active low frequency (1 Hz) rTMS or sham-placebo) applied to the Supplementary Motor Area (SMA) daily for up to four weeks. If rTMS will be added onto ongoing pharmacotherapy, the doses must have been stable for 3 months prior to study entry. The SMA was selected because of its connections with areas of the brain, especially motor areas, implicated in OCD. Pilot work indicates that stimulation of SMA with low frequency rTMS was beneficial in OCD patients. Low frequency rTMS has the added benefit of a better safety profile (i.e. no risk of seizure) compared to high frequency rTMS.

Rating scales for symptom change will be obtained at baseline, during the rTMS course, and at the end of 4 weeks of treatment. Patients who do not meet response criteria after four weeks of sham and partial responders to either active or sham will be offered an open-label, cross-over phase for an additional four weeks of daily active rTMS treatment. Patients who meet response criteria in either the randomized phase or the cross-over phase will continue routine clinical care under the supervision of their treating psychiatrist, and will be invited back for a repeat assessment at 3 and 6 months to determine the persistence of benefit.

Measures of the excitability of the motor cortex have been reported to be abnormal in OCD, and may relate to dysfunction in motor pathways related to OCD circuits. We will collect measures of motor cortex excitability (performed with single pulse TMS) at baseline and after treatment to determine whether changes in these measures may be correlated with clinical improvement.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary diagnosis of obsessive compulsive disorder, with residual OCD symptoms, defined as a total Y-BOCS score of ≥ 16, despite treatment with an adequate trial of a serotonin reuptake inhibitor (SRI), and a duration of the index episode of at least a year will be included. An adequate SRI trial is defined as treatment for at least 12 weeks on the SRI, that meets or exceeds the recommended dosage level for OCD (fluoxetine 60 mg/d, sertraline 200 mg/d, paroxetine 50 mg/d, fluvoxamine 250 mg/d, citalopram 60 mg/d, escitalopram 30 mg/d).
  • Individuals who cannot tolerate medications of class and dose at the specified duration as described above will also be included.
  • Patients currently on OCD medication must be at the same stable dose(s) and must continue to be under the care of their treating psychiatrist who will be writing prescriptions for concomitant medications through the duration of the study.

Exclusion Criteria:

  • Refractory patients, where treatment refractoriness is defined as non-response to Clomipramine, at least 2 SSRIs at adequate dose and duration plus cognitive behavior therapy in the last year, will be excluded. An adequate trial of cognitive behavioral therapy is defined as at least once a week for 8 weeks with clear evidence of exposure during the sessions and homework given. Individuals diagnosed with major depressive disorder (current) of moderate or severe intensity (CGI ≥ 4), and those with bipolar disorder (lifetime), any psychotic disorder (lifetime), history of substance abuse or dependence within the past year (except nicotine and caffeine), and at significant acute suicide risk will also be excluded.

Other exclusion criteria include those common to every TMS protocol:

  • Individuals with a clinically defined neurological disorder, with an increased risk of seizure for any reason, with a history of treatment with TMS, deep brain stimulation for any disorder will be excluded.
  • Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded.
  • Current use of any investigational drug will not be permitted.
  • If participating in psychotherapy, patients must have been in stable treatment for at least three months prior to entry into the study, with no anticipation of change in frequency therapeutic sessions, or the therapeutic focus over the duration of the TMS trial.
  • Finally, current significant laboratory abnormality, known or suspected pregnancy, women who are breast-feeding or women of childbearing potential not using a medically accepted form of contraception when engaging in sexual intercourse will also be excluded.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00106249


Locations
United States, New York
New York State Psychiatric Institute, Experimental Therapeutics
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Antonio Mantovani, MD, PhD Columbia University
  More Information

Publications:
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00106249     History of Changes
Other Study ID Numbers: 5926R
First Submitted: March 21, 2005
First Posted: March 22, 2005
Results First Submitted: September 6, 2016
Results First Posted: January 27, 2017
Last Update Posted: January 27, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by New York State Psychiatric Institute:
TMS, Supplementary Motor Area, Obsessive-Compulsive Disorder

Additional relevant MeSH terms:
Disease
Compulsive Personality Disorder
Obsessive-Compulsive Disorder
Pathologic Processes
Personality Disorders
Mental Disorders
Anxiety Disorders