Transcranial Magnetic Stimulation (TMS) and Obsessive Compulsive Disorder (OCD)
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:
- 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).
- 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.
Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Treatment of Obsessive Compulsive Disorder (OCD) With Transcranial Magnetic Stimulation (TMS)|
- Clinical Improvement (Yale-Brown Obsessive Compulsive Scale, Clinical Global Impression) [ Time Frame: Weekly ] [ Designated as safety issue: No ]
- Motor Cortex Excitability Normalization (increased intracortical inhibition, motor threshold, and cortical silent period, and decreased intracortical facilitation, relative to pre-treatment baseline) [ Time Frame: Bi-weekly ] [ Designated as safety issue: No ]
- Clinical Improvement (Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Zung Self-Rating Anxiety Scale, Symptom Check-List, Social Adaptation Self-evaluation Scale) [ Time Frame: Weekly ] [ Designated as safety issue: No ]
|Study Start Date:||November 2004|
|Estimated Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
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)
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00106249
|Contact: Clinic Coordinator||646-774-8077|
|Contact: Antonio Mantovani, MD, PhDemail@example.com|
|United States, New York|
|New York State Psychiatric Institute, Experimental Therapeutics||Recruiting|
|New York, New York, United States, 10032|
|Contact: Antonio Mantovani, MD, PhD 646-774-5418 firstname.lastname@example.org|
|Contact: Helen B. Simpson, MD, PhD 646-774-8110 email@example.com|
|Principal Investigator: Antonio Mantovani, MD, PhD|
|Sub-Investigator: Joshua Berman, MD, PhD|
|Sub-Investigator: Helen B. Simpson, MD, PhD|
|Sub-Investigator: Laurence Kegeles, MD, PhD|
|Principal Investigator:||Antonio Mantovani, MD, PhD||Columbia University|