Transcranial Magnetic Stimulation (TMS) and Obsessive Compulsive Disorder (OCD) - Full Text View

Sponsored by:	New York State Psychiatric Institute
Information provided by:	New York State Psychiatric Institute
ClinicalTrials.gov Identifier:	NCT00106249

Purpose

This study will evaluate the clinical efficacy of 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. We will collect TMS measures of motor cortex excitability to test whether rTMS restores normal levels of intracortical inhibition found to be deficient in OCD. We 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.

Condition	Intervention	Phase
Obsessive-Compulsive Disorder	Device: Transcranial Magnetic Stimulation (TMS)	Phase II

MedlinePlus related topics: Anxiety Obsessive-Compulsive Disorder

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	Treatment of Obsessive Compulsive Disorder (OCD) With Transcranial Magnetic Stimulation (TMS)

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

Primary Outcome Measures:

Clinical Improvement (Yale-Brown Obsessive Compulsive Scale, Clinical Global Impression)
Motor Cortex Excitability Normalization (increased intracortical inhibition, motor threshold, and cortical silent period, and decreased intracortical facilitation, relative to pre-treatment baseline)

Secondary Outcome Measures:

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)

Estimated Enrollment:	20
Study Start Date:	November 2004
Estimated Study Completion Date:	April 2008

Detailed Description:

This study tests the efficacy of 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, 20 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 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

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
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, any medications with proconvulsive action, such as bupropion, maprotiline, tricyclic antidepressant, clomipramine, classical antipsychotics, and daily use of any medications with a known inhibitory effect on cortical excitability measures (e.g., anticonvulsants, standing doses of benzodiazepines, sedative/hypnotics, and atypical antipsychotics) 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00106249

Locations

United States, New York
New York State Psychiatric Institute, Biological Psychiatry
New York, New York, United States, 10032

Sponsors and Collaborators

New York State Psychiatric Institute

Investigators

Principal Investigator:	Antonio Mantovani, MD	Columbia University
Study Chair:	Sarah H. Lisanby, MD	Columbia University

More Information

Publications:

Maeda F, Pascual-Leone A. Transcranial magnetic stimulation: studying motor neurophysiology of psychiatric disorders. Psychopharmacology (Berl). 2003 Aug;168(4):359-76. Epub 2003 Jun 26. Review.

Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol. 2002 Mar;5(1):73-103.

Rossi S, Bartalini S, Ulivelli M, Mantovani A, Di Muro A, Goracci A, Castrogiovanni P, Battistini N, Passero S. Hypofunctioning of sensory gating mechanisms in patients with obsessive-compulsive disorder. Biol Psychiatry. 2005 Jan 1;57(1):16-20.

Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Int J Neuropsychopharmacol. 2006 Feb;9(1):95-100. Epub 2005 Jun 28.

Study ID Numbers:	4828
Study First Received:	March 21, 2005
Last Updated:	August 23, 2007
ClinicalTrials.gov Identifier:	NCT00106249
Health Authority:	United States: Institutional Review Board

Keywords provided by New York State Psychiatric Institute:

TMS, Supplementary Motor Area, Obsessive-Compulsive Disorder

Study placed in the following topic categories:

Anxiety Disorders
Mental Disorders
Obsessive-Compulsive Disorder

Additional relevant MeSH terms:

Pathologic Processes
Disease

ClinicalTrials.gov processed this record on January 15, 2009