Repetitive Transcranial Magnetic Stimulation in Obsessive Compulsive Disorder

University Hospital, Grenoble56 enrolled

Overview

Evaluate the therapeutic effect of a functional Magnetic Resonance Imaging (fMRI)-guided and robotized neuronavigated theta burst Transcranial Magnetic Stimulation (TMS) targeting right inferior frontal region in resistant obsessive compulsive disorder (OCD) in a double-blind, randomized, placebo-controlled, monocentric study.

This study evaluates the therapeutic effect of a fMRI-guided and robotized neuronavigated theta burst Transcranial Magnetic Stimulation (TMS) targeting right inferior frontal region in resistant obsessive compulsive disorder (OCD) in a double-blind, randomized, placebo-controlled, monocentric study. The study will also assess the interest of some clinical, neuropsychological, neuroimaging, electrophysiological variables in response prediction, besides physiopathological information. There is an increasing interest in developping treatments for resistant OCD, which are not responding to the conventional treatment, represented by pharmacotherapy associated to cognitive behavioral therapy. Repetitive TMS represents a promising non invasive brain stimulation approach, but efficacy, best available brain target, optimal responder profile and stimulation parameters need to be further documented. In this study, the included patients will be randomly assigned to an active (theta burst TMS) or sham-placebo treatment group. TMS will be added to their stable pharmacotherapy. The brain target, the right inferior frontal region, involved in the inhibition control brain network, will be defined in a personalized manner via a fMRI paradigm for each patient. TMS will be delivered daily for 2 successive weeks. Measures of different clinical, neuropsychological , electrophysiological (cortical excitability) variables will be performed at baseline, as well as at the end of the TMS course, and 1 week after. Other assessments are planned at 3 and 6 months, in order to highlight the evolution of the potential benefit.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Obsessive-Compulsive Disorder

Interventions

Active Repetitive Transcranial Magnetic StimulationDEVICE

modulation of the electrical activity of the right inferior frontal gyrus cortex in order to reduce Obsessive Compulsive Disorders symptoms by Active Transcranial Magnetic Stimulation (TMS) targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, using theta burst stimulation and using a TMS neuronavigated robot

Placebo Repetitive Transcranial Magnetic StimulationDEVICE

Sham rTMS will be delivered using non active magnetic coil, targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, using TMS neuronavigated robot. A subjective sensation will be obtained via frontal dermic electrical stimulation.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Volunteer subjects with Obsessive Compulsive Disorders (OCD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) criteria and validated by an experimented clinician following instruments like SCID (Structured Clinical Interview for DSM IV) or MINI (Mini-International Neuropsychiatric Interview) * with or without associated tics ("Gilles de la Tourette" Syndrome) * Age \> 18 years old * Y-BOCS score \> 20 and CGI (Clinical Global Impression Scale) score ≥ 4 * Resistant patients to standard treatments - where treatment resistance is defined by partial but insufficient response (Global Assessment of Functioning score GAF score \< 60 and/or reduction of Yale Brown Obsessions and Compulsion Scale score \< 35%) or lack of response to previous well conducted treatment including: * pharmacotherapy : optimal tolerated dose and adequate duration (\> 12 weeks) of at least 2 Serotonin Reuptake Inhibitors (selective serotonin reuptake inhibitors, clomipramine), and one augmentation strategy (adjunction of an antipsychotic - such as risperidone or olanzapine or aripiprazole - or lithium or buspirone) ; * psychotherapy (at least 6 months of cognitive and behavioral therapy) Exclusion Criteria: * other primary diagnosis than OCD (comorbid tics and depression are tolerated) * comorbid diagnosis of schizophrenia/ psychotic disorder, bipolar disorder, substance abuse or dependance * medical condition involving cognitive decline and affecting brain structures such as Parkinson disease, dementia, multiple sclerosis, HIV (human immunodeficiency virus) infection, lupus etc. * Magnetic Resonance Imaging exclusion criteria (ferromagnetic implants etc) * common TMS exclusion criteria (neurological condition with an increased risk of seizure, cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, intracranial implants (e.g. cochlear implants, electrodes, aneurysm clips, stimulators... ) 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 * pregnancy / breast feeding patients * visual or auditive important deficit

Locations (1)

CHU de Grenoble - Pavillon Dominique Villars

Grenoble, Auvergne-Rhône-Alpes, France

RECRUITING

Outcomes

Primary Outcomes

Change from baseline of the score at the Yale - Brown Obsessive and Compulsive Scale

Evaluation of Obsessive Compulsive Disorder symptoms using the Yale - Brown Obsessive and Compulsive Scale, at day 21, corresponding to 7 days after the end of the TMS cure, compared to baseline.

Time frame: at baseline and at day 21

Secondary Outcomes

Score of Montgomery and Asberg Depression Rating Scale, as a Measure of effects on Mood (depression)

Evaluation of Mood using Montgomery Asberg Depression Rating Scale

Time frame: At baseline, at day 21, day 90, day 180

Score of Young Mania Rating Scale, as a Measure of effects on Mood (hyperthymia)

Evaluation of Mood using Young Mania Rating Scale

Time frame: At baseline, at day 21, day 90, day 180

Score of Multidimensional Assessment of Thymic States Scale as a Measure of effects on Emotional Reactivity

Evaluation of Emotional Reactivity using Multidimensional Assessment of Thymic States Scale

Time frame: At baseline, at day 21, day 90, day 180

Number of patients with Side effects as a measure of Safety and Tolerability

collection of the side effects of the Transcranial Magnetic Stimulation, after each session, during the entire TMS cure

Time frame: for each session of Transcranial Magnetic Stimulation, at day 15, day 21, day 90, day 180

Inferior Frontal Region Activity (percentage of the BOLD signal change (parameter estimates beta)

Performing a functional Magnetic Resonance Imaging, looking for biomarkers of response to the TMS cure. Especially studying the right inferior cortex activation in functional Magnetic Resonance Imaging using a Signal Stop Task.

Central Contacts

Mircea POLOSAN, Professor

CONTACT

mpolosan@chu-grenoble.fr

Data from ClinicalTrials.gov

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