Repetitive Transcranial Magnetic Stimulation in Obsessive Compulsive Disorder

Stimulation magnétique transcrânienne répétitive Dans le Traitement Des Troubles Obsessionnels Compulsifs

Sponsors

Lead Sponsor: University Hospital, Grenoble

Source University Hospital, Grenoble
Brief Summary

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.

Detailed Description

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.

Overall Status Recruiting
Start Date May 2015
Completion Date May 2021
Primary Completion Date November 2019
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Change from baseline of the score at the Yale - Brown Obsessive and Compulsive Scale at baseline and at day 21
Secondary Outcome
Measure Time Frame
Score of Montgomery and Asberg Depression Rating Scale, as a Measure of effects on Mood (depression) At baseline, at day 21, day 90, day 180
Score of Young Mania Rating Scale, as a Measure of effects on Mood (hyperthymia) 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 At baseline, at day 21, day 90, day 180
Number of patients with Side effects as a measure of Safety and Tolerability 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) at baseline (day 0)
Fractional Anisotropy (FA), mean and radial diffusivity (MD, RD), tracti integrity of the inhibition network, at day 0 (baseline)
Yale - Brown Obsessive and Compulsion Scale score after the TMS treatment as an evaluation of the persistence of the clinical benefit day 15, day 90 and day 180 after the inclusion.
Cortical Excitability baseline - day 15 - day 21 - day 90 - day 180
Evaluation of Impulsivity using specific scales At baseline, at day 21, day 90, day 180
Evaluation of the Clinical global State at baseline, day 15, day 21, day 90, day 180
type of side effects (pain, paresthesia, other) as a measure of Safety and Tolerability for each session of Transcranial Magnetic Stimulation, at day 15, day 21, day 90, day 180
Enrollment 56
Condition
Intervention

Intervention Type: Device

Intervention Name: Active Repetitive Transcranial Magnetic Stimulation

Description: 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

Arm Group Label: active Transcranial Magnetic Stimulation

Intervention Type: Device

Intervention Name: Placebo Repetitive Transcranial Magnetic Stimulation

Description: 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.

Arm Group Label: Placebo

Eligibility

Criteria:

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Mircea POLOSAN, Professor Principal Investigator Institut National de la Santé Et de la Recherche Médicale, France
Overall Contact

Last Name: Mircea POLOSAN, Professor

Email: [email protected]

Location
Facility: Status: Contact: CHU de Grenoble - Pavillon Dominique Villars POLOSAN Mircea, Professor [email protected]
Location Countries

France

Verification Date

May 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: active Transcranial Magnetic Stimulation

Type: Active Comparator

Description: 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 Transcranial Magnetic Stimulation navigator and robot

Label: Placebo

Type: Placebo Comparator

Description: Placebo comparator, using non active magnetic coil, targeting the right frontal inferior gyrus, 2 sessions per day, each session 5min30 day, during 10 consecutive days, using theta burst stimulation and using Transcranial Magnetic Stimulation navigator and robot

Acronym MAGTOC
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov