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Neurostimulation and OCD, a MRI Study (ASLTOC)

Primary Purpose

Obsessive Compulsive Disorder

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Sham rTMS
Active rTMS
Sponsored by
Hospital Center Guillaume Régnier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Obsessive Compulsive Disorder focused on measuring Arterial Spin Labeling, Obsessive Compulsive Disorder, Magnetic Resonance Imaging, Repetitive Transcranial Magnetic Stimulation, Double blinded, Sham

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre Hospitalier Guillaume Régnier

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Active Comparator

Arm Label

Sham rTMS

Active rTMS

Arm Description

The investigators will perform sham rTMS at 30% of the Motor Threshold, with a 1Hz frequency and 1200 pulses during one session. The target will be the right Orbito Frontal Cortex, localized using Neuronavigation. Sessions will last fifteen minutes; subjects will perform two sessions a day during five days. The coil will have a 180° rotation compared to the active coil position, thus making the magnetic field ineffective on the patient's cortex. Participants will undergo a MRI with anatomical and ASL sequences one week before and four weeks after treatment. All participants of this group will have the opportunity to undergo an active rTMS treatment right after the end of each one's participation in the study.

The investigators will perform active rTMS at 120% of the Motor Threshold, with a 1Hz frequency and 1200 pulses during one session. The target will be the right Orbito Frontal Cortex, localized using Neuronavigation. Sessions will last fifteen minutes; subjects will perform two sessions a day during five days. Participants will undergo a MRI with anatomical and ASL sequences one week before and four weeks after treatment

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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).
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.
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.

Full Information

First Posted
April 11, 2019
Last Updated
August 5, 2022
Sponsor
Hospital Center Guillaume Régnier
Collaborators
Fondation de l'Avenir
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1. Study Identification

Unique Protocol Identification Number
NCT03918837
Brief Title
Neurostimulation and OCD, a MRI Study
Acronym
ASLTOC
Official Title
Effects of rTMS Over Right COF Blood Perfusion in OCD Patients: an ASL Double Blinded Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
April 26, 2019 (Actual)
Primary Completion Date
June 24, 2022 (Actual)
Study Completion Date
June 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Center Guillaume Régnier
Collaborators
Fondation de l'Avenir

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obsessive Compulsive Disorder
Keywords
Arterial Spin Labeling, Obsessive Compulsive Disorder, Magnetic Resonance Imaging, Repetitive Transcranial Magnetic Stimulation, Double blinded, Sham

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sham rTMS
Arm Type
Sham Comparator
Arm Description
The investigators will perform sham rTMS at 30% of the Motor Threshold, with a 1Hz frequency and 1200 pulses during one session. The target will be the right Orbito Frontal Cortex, localized using Neuronavigation. Sessions will last fifteen minutes; subjects will perform two sessions a day during five days. The coil will have a 180° rotation compared to the active coil position, thus making the magnetic field ineffective on the patient's cortex. Participants will undergo a MRI with anatomical and ASL sequences one week before and four weeks after treatment. All participants of this group will have the opportunity to undergo an active rTMS treatment right after the end of each one's participation in the study.
Arm Title
Active rTMS
Arm Type
Active Comparator
Arm Description
The investigators will perform active rTMS at 120% of the Motor Threshold, with a 1Hz frequency and 1200 pulses during one session. The target will be the right Orbito Frontal Cortex, localized using Neuronavigation. Sessions will last fifteen minutes; subjects will perform two sessions a day during five days. Participants will undergo a MRI with anatomical and ASL sequences one week before and four weeks after treatment
Intervention Type
Other
Intervention Name(s)
Sham rTMS
Intervention Description
Participants will undergo sham rTMS for five days with two daily fifteen minutes rTMS sessions.
Intervention Type
Other
Intervention Name(s)
Active rTMS
Intervention Description
Participants will undergo active rTMS for five days with two daily fifteen minutes rTMS sessions.
Primary Outcome Measure Information:
Title
Cerebral Blood Flow of the Orbito-Frontal Cortex from Arterial Spin Labeling Data
Description
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.
Time Frame
one measure four weeks after end of treatment
Secondary Outcome Measure Information:
Title
Score at Yale-Brown Obsessive Compulsive Scale (YBOCS)
Description
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.
Time Frame
one measure before treatment, one four weeks after end of treatment
Title
Score at Montgomery and Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
one measure before treatment, one four weeks after end of treatment
Title
Score at General Assessment Functioning Scale (GAF)
Description
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.
Time Frame
one measure before treatment, one four weeks after end of treatment
Title
Score at Hamilton Anxiety Rating Scale (HAMA)
Description
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.
Time Frame
one measure before treatment, one four weeks after end of treatment
Title
Blindness Evaluation
Description
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).
Time Frame
measure will occur four weeks after the treatment, at the same assessment than clinical outcomes
Title
Intra Group CBF Comparison
Description
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.
Time Frame
one measure before treatment, one four weeks after end of treatment
Title
Score at Clinical Global Impression scale (CGI)
Description
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.
Time Frame
one measure before treatment, one four weeks after end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dominique DRAPIER, MD PHD
Organizational Affiliation
Centre Hospitalier Guillaume Régnier
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Guillaume Régnier
City
Rennes
State/Province
Ille Et Vilaine
ZIP/Postal Code
35000
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data about study protocol and clinical information will be available on request from other researchers. MRI raw data will not be shared but processed data is planned to be available.
IPD Sharing Time Frame
Data will be available from the moment a scientific publication is accepted to 5 years later.
IPD Sharing Access Criteria
Access to data will be granted for researchers aiming to perform another analysis or to review the topic, or to perform a meta-analysis.
Citations:
PubMed Identifier
24314349
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.
Results Reference
result
PubMed Identifier
29234089
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.
Results Reference
result
PubMed Identifier
20951978
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.
Results Reference
result
PubMed Identifier
25203167
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.
Results Reference
result
PubMed Identifier
19956460
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.
Results Reference
result

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Neurostimulation and OCD, a MRI Study

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