Obsessive-Compulsive Disorder
Conditions
Keywords
Obsessive-Compulsive Disorder, Transcranial Magnetic Stimulation
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.
Interventions
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
DEVICEPlacebo Repetitive Transcranial Magnetic Stimulation
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.
Sponsors
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline of the score at the Yale - Brown Obsessive and Compulsive Scale | at baseline and at day 21 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score of Young Mania Rating Scale, as a Measure of effects on Mood (hyperthymia) | At baseline, at day 21, day 90, day 180 | Evaluation of Mood using Young Mania Rating Scale |
| 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 | Evaluation of Emotional Reactivity using Multidimensional Assessment of Thymic States Scale |
| 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 | collection of the side effects of the Transcranial Magnetic Stimulation, after each session, during the entire TMS cure |
| Inferior Frontal Region Activity (percentage of the BOLD signal change (parameter estimates beta) | at baseline (day 0) | 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. |
| Fractional Anisotropy (FA), mean and radial diffusivity (MD, RD), tracti integrity of the inhibition network, | at day 0 (baseline) | looking for anatomical biomarkers of response, or anatomical differences between the subjects on the inhibition network using Diffusing Tensor Imaging data |
| 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 | Evaluation of Mood using Montgomery Asberg Depression Rating Scale |
| Cortical Excitability | baseline - day 15 - day 21 - day 90 - day 180 | assessing a new biomarker linked to OCD and monitoring its evolution with the TMS cure, testing its predictive value for the clinical response |
| Evaluation of Impulsivity using specific scales | At baseline, at day 21, day 90, day 180 | Evaluation of impulsivity using UPPS (Urgency, Premeditation, and Sensation Seeking) Impulsive Behavior Scale. |
| Evaluation of the Clinical global State | at baseline, day 15, day 21, day 90, day 180 | Using Clinical Global Impression scale we will assess the evolution of the clinical global status |
| 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 | collection of the side effects of the Transcranial Magnetic Stimulation, after each session, during the entire TMS cure |
| 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. | The Yale - Brown Obsessive and Compulsion Scale will also be performed at day 15, day 90 and day 180 after the inclusion in order to assess the kinetics of clinical changes in Obsessive Compulsive symptoms after the TMS cure. |
Countries
France
Contacts
Primary ContactMircea POLOSAN, Professor
Outcome results
None listed