Neurostimulation and OCD, a MRI Study

Obsessive Compulsive Disorder Clinical Trial

— ASLTOC  

Official title:

Effects of rTMS Over Right COF Blood Perfusion in OCD Patients: an ASL Double Blinded Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03918837
• Other study ID #: RC19_01DD_ASLTOC
• Status: Completed
• Phase: N/A
• Start date: April 26, 2019
• Est. completion date: June 24, 2022

Study information

• Verified date: August 2022
• Source: Hospital Center Guillaume Régnier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 24, 2022
• Est. primary completion date: June 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Obsessive Compulsive Disorder
• Obsessive-Compulsive Disorder

Intervention

Other:
• Sham rTMS
Participants will undergo sham rTMS for five days with two daily fifteen minutes rTMS sessions.
• Active rTMS
Participants will undergo active rTMS for five days with two daily fifteen minutes rTMS sessions.

Locations

Country	Name	City	State
France	Centre Hospitalier Guillaume Régnier	Rennes	Ille Et Vilaine

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Center Guillaume Régnier	Fondation de l'Avenir

Country where clinical trial is conducted

France, 

References & Publications (5)

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 cerebell — View Citation

Le Jeune F, Vérin 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 — View Citation

Nauczyciel C, Le Jeune F, Naudet F, Douabin S, Esquevin A, Vérin 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. T — View 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. Pr — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cerebral Blood Flow of the Orbito-Frontal Cortex from Arterial Spin Labeling Data	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.	one measure four weeks after end of treatment
Secondary	Score at Yale-Brown Obsessive Compulsive Scale (YBOCS)	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.	one measure before treatment, one four weeks after end of treatment
Secondary	Score at Montgomery and Asberg Depression Rating Scale (MADRS)	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.	one measure before treatment, one four weeks after end of treatment
Secondary	Score at General Assessment Functioning Scale (GAF)	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.	one measure before treatment, one four weeks after end of treatment
Secondary	Score at Hamilton Anxiety Rating Scale (HAMA)	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.	one measure before treatment, one four weeks after end of treatment
Secondary	Blindness Evaluation	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).	measure will occur four weeks after the treatment, at the same assessment than clinical outcomes
Secondary	Intra Group CBF Comparison	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.	one measure before treatment, one four weeks after end of treatment
Secondary	Score at Clinical Global Impression scale (CGI)	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.	one measure before treatment, one four weeks after end of treatment