Obsessive Compulsive Disorder
Conditions
Keywords
Arterial Spin Labeling, Obsessive Compulsive Disorder, Magnetic Resonance Imaging, Repetitive Transcranial Magnetic Stimulation, Double blinded, Sham
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.
Interventions
OTHERSham rTMS
Participants will undergo sham rTMS for five days with two daily fifteen minutes rTMS sessions.
OTHERActive rTMS
Participants will undergo active rTMS for five days with two daily fifteen minutes rTMS sessions.
Sponsors
Fondation de l'Avenir
Hospital Center Guillaume Régnier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The masking model will use the same rTMS coil as the active group, bit with a 180° rotation, making the magnetic field face the opposite direction, and thus not being able to produce Neuromodulation on the patient. The stimulation intensity will be decreased at 30% of the motor threshold, to keep the characteristic sound of active rTMS. The patient will not know their group; neither will the investigator nor the rater. Only the rTMS performing technician will know the randomization group to be able to choose the right setting.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Blood Flow of the Orbito-Frontal Cortex from Arterial Spin Labeling Data | one measure four weeks after end of treatment | Comparison between the sham rTMS group and the active rTMS group will be analyzed from the ASL data about cerebral blood flow in the Orbito-Frontal Cortex. We expect to find a significant difference between the two groups four weeks after the treatment on the mean of cerebral blood flow, as raw data will be converted into numerical data for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Score at Montgomery and Asberg Depression Rating Scale (MADRS) | one measure before treatment, one four weeks after end of treatment | MADRS is a clinical scale used to measure the severity of depressive symptoms for a patient, ranging from 0 to 60 (maximum severity), analyzes will be based on each group's mean score. |
| Score at General Assessment Functioning Scale (GAF) | one measure before treatment, one four weeks after end of treatment | GAF is a scale representing the functional abilities of a patient in his daily life and the way his illness potentially impairs his normal social, personal and professional quality of life, ranging from 0 to 100 (representing a normal fully functioning life), analyzes will be based on each group's mean score. |
| Score at Hamilton Anxiety Rating Scale (HAMA) | one measure before treatment, one four weeks after end of treatment | HAMA is a scale used to measure the intensity of anxious symptoms of a patient at a given time, ranging from 0 to 60 (maximum severity), analyzes will be based on each group's mean score. |
| Score at Yale-Brown Obsessive Compulsive Scale (YBOCS) | one measure before treatment, one four weeks after end of treatment | YBOCS is a scale used to make an accurate and objective measure of the intensity of OCD symptoms for a patient at a precise time, ranging from 0 to 40 (maximum severity), analyzes will be based on each group's mean score. |
| Intra Group CBF Comparison | one measure before treatment, one four weeks after end of treatment | We will be using the ASL data to compare the evolution of cerebral blood flow in the Orbito-Frontal Cortex within each patient's brain. |
| Score at Clinical Global Impression scale (CGI) | one measure before treatment, one four weeks after end of treatment | CGI is a scale used to give a clinical impression of a patient from the physician's observation, being able to evaluate if the patient's condition has worsened or improved between two evaluations, scores ranging from 0 to 7 (maximum severity or important degradation of the patient's condition), analyzes will be based on each group's mean score. |
| Blindness Evaluation | measure will occur four weeks after the treatment, at the same assessment than clinical outcomes | Participants will pass an evaluation of their perception of the sham devices, which will allow us to analyze the masking strategy the investigators use considering this double blind study. A five propositions assessment will be used, ranging from 1 to 5 (1 representing the patient's certainty of being in the active treatment group and 5 representing the patient's certainty of being in the sham treatment group). Analyses will be carried using Bang's Blinding Index (Bang et al, Assessment of blinding in clinical trials. Control Clin Trials. 2004). |
Countries
France
Outcome results
None listed