Transcranial Magnetic Stimulation (TMS) and Obsessive Compulsive Disorder (OCD)
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Repetitive Transcranial Magnetic Stimulation (rTMS); Sham
Intervention type(s): Device; Device
Intervention description(s): 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.; 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.
Other intervention name(s): Magstim Rapid2, Magstim SuperRapid, Magstim Rapid, Magstim
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: TMS, Supplementary Motor Area, Obsessive-Compulsive Disorder