search
Back to results

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

Primary Purpose

Obsessive-Compulsive Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Repetitive Transcranial Magnetic Stimulation (rTMS)
Sham
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obsessive-Compulsive Disorder focused on measuring TMS, Supplementary Motor Area, Obsessive-Compulsive Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • New York State Psychiatric Institute, Experimental Therapeutics

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Active rTMS

Sham rTMS

Arm Description

Active Repetitive Transcranial Magnetic Stimulation (rTMS)

Placebo Repetitive Transcranial Magnetic Stimulation (rTMS)

Outcomes

Primary Outcome Measures

Clinical Improvement (Yale-Brown Obsessive Compulsive Scale/Y-BOCS)
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)
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)
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.

Full Information

First Posted
March 21, 2005
Last Updated
December 1, 2016
Sponsor
New York State Psychiatric Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT00106249
Brief Title
Transcranial Magnetic Stimulation (TMS) and Obsessive Compulsive Disorder (OCD)
Official Title
Treatment of Obsessive Compulsive Disorder (OCD) With Transcranial Magnetic Stimulation (TMS)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
November 2004 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New York State Psychiatric Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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: 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive-Compulsive Disorder
Keywords
TMS, Supplementary Motor Area, Obsessive-Compulsive Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active rTMS
Arm Type
Active Comparator
Arm Description
Active Repetitive Transcranial Magnetic Stimulation (rTMS)
Arm Title
Sham rTMS
Arm Type
Sham Comparator
Arm Description
Placebo Repetitive Transcranial Magnetic Stimulation (rTMS)
Intervention Type
Device
Intervention Name(s)
Repetitive Transcranial Magnetic Stimulation (rTMS)
Other Intervention Name(s)
Magstim Rapid2, Magstim SuperRapid, Magstim Rapid, Magstim
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical Improvement (Yale-Brown Obsessive Compulsive Scale/Y-BOCS)
Description
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.
Time Frame
Through study completion
Secondary Outcome Measure Information:
Title
Motor Cortex Excitability (Motor Threshold)
Description
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.
Time Frame
Through study completion
Title
Motor Cortex Excitability (Short Intracortical Inhibition)
Description
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.
Time Frame
Through study completion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Mantovani, MD, PhD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute, Experimental Therapeutics
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
12830365
Citation
Maeda F, Pascual-Leone A. Transcranial magnetic stimulation: studying motor neurophysiology of psychiatric disorders. Psychopharmacology (Berl). 2003 Aug;168(4):359-76. doi: 10.1007/s00213-002-1216-x. Epub 2003 Jun 26.
Results Reference
background
PubMed Identifier
12057034
Citation
Burt T, Lisanby SH, Sackeim HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol. 2002 Mar;5(1):73-103. doi: 10.1017/S1461145702002791.
Results Reference
background
PubMed Identifier
15607295
Citation
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. doi: 10.1016/j.biopsych.2004.09.023.
Results Reference
background
PubMed Identifier
19691873
Citation
Mantovani A, Simpson HB, Fallon BA, Rossi S, Lisanby SH. Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2010 Mar;13(2):217-27. doi: 10.1017/S1461145709990435. Epub 2009 Aug 20.
Results Reference
background
PubMed Identifier
19793582
Citation
Mantovani A, Westin G, Hirsch J, Lisanby SH. Functional magnetic resonance imaging guided transcranial magnetic stimulation in obsessive-compulsive disorder. Biol Psychiatry. 2010 Apr 1;67(7):e39-40. doi: 10.1016/j.biopsych.2009.08.009. Epub 2009 Sep 30. No abstract available.
Results Reference
background
PubMed Identifier
15982444
Citation
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. doi: 10.1017/S1461145705005729. Epub 2005 Jun 28.
Results Reference
background

Learn more about this trial

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

We'll reach out to this number within 24 hrs