Clinical trial NCT03918837: Neurostimulation and OCD, a MRI Study
Official title: Effects of rTMS Over Right COF Blood Perfusion in OCD Patients: an ASL Double Blinded Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obsessive Compulsive Disorder
Keywords: Arterial Spin Labeling
Obsessive Compulsive Disorder
Magnetic Resonance Imaging
Repetitive Transcranial Magnetic Stimulation
Double blinded
Sham
Lead sponsor: Hospital Center Guillaume Régnier
Sponsor class: OTHER
Collaborators: name: Fondation de l'Avenir
First posted: 2019-04-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The investigators will randomize participants between two parallel groups using a randomization list. One group will undergo active rTMS while the second one will undergo sham rTMS. The second group will have the possibility of performing an active rTMS treatment at the end of each patient's participation. All subjects will undergo a MRI with anatomical and ASL sequences one week before treatment and four weeks after treatment.
Primary purpose: OTHER

Brief summary: This study will focus on the use of repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment of Obsessive Compulsive Disorder (OCD), which is a common illness that impairs quality of life and that can be hard to treat.

To precisely analyze the effects of rTMS on OCD, the investigators are going to plan a study comparing cerebral blood flow before and after rTMS treatment. The measuring will occur on the Orbito Frontal Cortex (OFC), whose role in OCD has already been shown by our team (Nauczyciel et al, 2014 in Translational Psychiatry), using Magnetic Resonance Imaging in Arterial Spin Labeling, an MRI method allowing to measure arteriola blood flow.

Our primary outcome is to show a significate difference between cerebral blood flow in OCD between one group of participants treated by rTMS and another one treated by placebo. The study will be double blinded with a placebo rTMS machine, monocentric and prospective, with participants suffering from OCD randomized between two groups.

Detailed description: Obsessive Compulsive Disorders (OCD) are a frequent and debilitating disease. Impact on daily life is usually important, with a high rate of mood and anxious comorbidities, such as Major Depressive Disorder occurring in half of these participants. The effects can be dramatic, leading to higher suicide rate in this population.

Guidelines for OCD treatment in France recommend the use of Serotonin Specific Recapture Inhibitors (SSRI) and Cognitive Behavioral Therapy (CBT), if possible simultaneously. However, those treatments are responsible for adverse effects for the first and not easily accessible for the second. Consequently, a non-negligible number of participants still suffers from symptoms of OCD with a non-optimal treatment.

Repetitive Transcranial Magnetic Stimulation (rTMS), a noninvasive neurostimulation method, has shown its usefulness in the treatment of mental illnesses. It has been authorized by the Food and Drugs Administration in the United States for the treatment of OCD. It represents an alternative method for helping those participants, but pattern of modifications over OCD pathophysiology has still to be unraveled.

In order to precisely analyze the effects of Low Frequency rTMS (LF rTMS) on OCD, the investigators designed a monocentric, prospective, double blind study comparing cerebral blood flow (CBF) before and after a rTMS treatment. Measurements will be performed on the Orbito Frontal Cortex (OFC), whose role in OCD has already been shown by our team (Nauczyciel et al, 2014 in Translational Psychiatry), using Magnetic Resonance Imaging (MRI) in Arterial Spin Labeling (ASL).

Inclusion criteria will be OCD diagnosis, age between 18 and 65, and the lack of counter indication to MRI and rTMS. Participants will firstly undergo MRI before treatment, along with a psychometric assessment. Participants will then receive a one-week rTMS treatment, with two sessions of fifteen minutes per day. Second MRI and evaluation will be performed 4 weeks after the end of the treatment.

Psychometric assessment will consist of MINI, YBOCS, CGI, MADRS, HAMA, and GAF, administered before and four weeks after treatment. The psychiatrist giving the assessment will be blind to the randomization of the patient, so will be the radiologist performing the MRI.

Our primary outcome is to show a significant difference between CBF in OCD in participants treated by rTMS versus participants treated by sham rTMS. A decrease of the CBF in the OFC is expected, in regards to the inhibitor effects of LF rTMS. This result will allow us to follow objectively the neurobiological effects of rTMS, developing the ability to plan more efficiently rTMS treatment for participants.

Eligibility criteria: Inclusion Criteria:

* Participants over 18 to 65
* Score at YBOCS over 15
* Diagnosis of Obsessive Compulsive Disorder acknowledged by two psychiatrists using the DSM V criteria
* Patient is able to receive and understand information about the trial, and agrees to participate in the trial
* Indication of treatment by rTMS

Exclusion Criteria:

Related to MRI and / or rTMS:

* Cardiac Stimulator or Implantable Automatic Defibrillator
* Neurosurgical Clips
* Cochlear Implant
* Intra ocular or cranial metallic foreign body
* Endoprosthesis lasting from less than four weeks
* Ostheosynthesis material lasting from less than six weeks
* Claustrophobia

Other criteria:

* Pregnancy or breast feeding
* Unstable hemodynamics, acute respiratory failure, need for constant surveillance not possible during the MRI, precarious general condition
* Patient over legal protection, care without consent
* Active psychiatric pathology other than anxious or mood disorder
* Active severe somatic disease
* History of seizures or other neurologic pathologies (Parkinson's Disease, CVA, Alzheimer's Disease, Multiple Sclerosis, Lewy Body Dementia...)
* Patient without social security

Primary outcomes:
measure: Cerebral Blood Flow of the Orbito-Frontal Cortex from Arterial Spin Labeling Data
timeFrame: one measure four weeks after end of treatment
Secondary outcomes:
measure: Score at Yale-Brown Obsessive Compulsive Scale (YBOCS)
timeFrame: one measure before treatment, one four weeks after end of treatment
measure: Score at Montgomery and Asberg Depression Rating Scale (MADRS)
timeFrame: one measure before treatment, one four weeks after end of treatment
measure: Score at General Assessment Functioning Scale (GAF)
timeFrame: one measure before treatment, one four weeks after end of treatment
measure: Score at Hamilton Anxiety Rating Scale (HAMA)
timeFrame: one measure before treatment, one four weeks after end of treatment
measure: Blindness Evaluation
timeFrame: measure will occur four weeks after the treatment, at the same assessment than clinical outcomes
measure: Intra Group CBF Comparison
timeFrame: one measure before treatment, one four weeks after end of treatment
measure: Score at Clinical Global Impression scale (CGI)
timeFrame: one measure before treatment, one four weeks after end of treatment
Other outcomes:
Locations:
city: Rennes
country: France
facility: Centre Hospitalier Guillaume Régnier
state: Ille Et Vilaine
Study officials:
affiliation: Centre Hospitalier Guillaume Régnier
name: Dominique DRAPIER, MD PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anticevic A, Hu S, Zhang S, Savic A, Billingslea E, Wasylink S, Repovs G, Cole MW, Bednarski S, Krystal JH, Bloch MH, Li CS, Pittenger C. Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry. 2014 Apr 15;75(8):595-605. doi: 10.1016/j.biopsych.2013.10.021. Epub 2013 Nov 4.
citation: van der Straten AL, Denys D, van Wingen GA. Impact of treatment on resting cerebral blood flow and metabolism in obsessive compulsive disorder: a meta-analysis. Sci Rep. 2017 Dec 12;7(1):17464. doi: 10.1038/s41598-017-17593-7.
citation: Le Jeune F, Verin M, N'Diaye K, Drapier D, Leray E, Du Montcel ST, Baup N, Pelissolo A, Polosan M, Mallet L, Yelnik J, Devaux B, Fontaine D, Chereau I, Bourguignon A, Peron J, Sauleau P, Raoul S, Garin E, Krebs MO, Jaafari N, Millet B; French Stimulation dans le trouble obsessionnel compulsif (STOC) study group. Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study. Biol Psychiatry. 2010 Dec 1;68(11):1016-22. doi: 10.1016/j.biopsych.2010.06.033. Epub 2010 Oct 16.
citation: Nauczyciel C, Le Jeune F, Naudet F, Douabin S, Esquevin A, Verin M, Dondaine T, Robert G, Drapier D, Millet B. Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study. Transl Psychiatry. 2014 Sep 9;4(9):e436. doi: 10.1038/tp.2014.62.
citation: Ruffini C, Locatelli M, Lucca A, Benedetti F, Insacco C, Smeraldi E. Augmentation effect of repetitive transcranial magnetic stimulation over the orbitofrontal cortex in drug-resistant obsessive-compulsive disorder patients: a controlled investigation. Prim Care Companion J Clin Psychiatry. 2009;11(5):226-30. doi: 10.4088/PCC.08m00663.