Coupling Repetitive Transcranial Magnetic Stimulation With a Neuronavigation System in Treatment Resistant Depression (TMS)

Assessment of the Neuronavigation System Coupled With Repetitive Transcranial Magnetic Stimulation. A Randomized Double Blind Study

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was shown to be effective in the treatment of major depression.

The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the standard (manual) '5-cm method' for positioning the coil over DLPFC is the reference. Nevertheless, it has been criticized due to poor targeting accuracies attributed to inter-subject variability.

Such an inaccuracy could have any therapeutic consequences as a decrease in rTMS efficacy.

Preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.

Investigator's objective is to compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.

Study Overview

• Status: Completed
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Device: Neuronavigation system; Device: Standard localisation method

Detailed Description

Background :

Repetitive Transcranial Magnetic Stimulation (rTMS) is a new tool for major depressive disorder.

rTMS is a non invasive technique allowing for a localized stimulation of cerebral tissue cortex. rTMS uses electromagnetic induction to induce weak electric currents using a rapidly changing magnetic field; this can modify activity in specific or general parts of the brain.

Meta-analyses have stated that rTMS appeared to be effective in the treatment of major depression despite any limits concerning sample sizes and methodological concerns.

Studies have shown that this technique potentiates antidepressants treatment in combination therapy.

It has received FDA approval for the management of major depressive disorder. Stimulation parameters are numerous (frequency, intensity, number of pulses) and their effects are increasingly better understood in order to predict a better balance between efficacy and tolerability.

The dorsolateral prefrontal cortex (DLPFC) is the target in repetitive transcranial magnetic stimulation and the standard (manual) '5-cm method' for positioning the transcranial magnetic stimulation coil over DLPFC is the reference. It has been criticized due to poor targeting accuracies attributed to inter-subject variability.

Such an inaccuracy could have consequences as a decrease in rTMS efficacy. Any preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.

Objectives:

To compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.

Investigators hypothesized that an accurate localization and stimulation of DLPFC using neuronavigation would be more effective than the less accurate standard method.

A secondary objective is to compare the efficacy on patient's self perception, on psychomotor symptoms and the tolerability of the two methods.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49130
    • Centre Santé Mentale Angevin CESAME
  • Brest, France, 29200
    • CHU de Brest
  • Quimperlé, France, 29300
    • Etablissement Public de Santé Mentale
  • Rennes, France, 35000
    • CHGR
  • St Avé, France, 56890
    • EPSM Morbihan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients giving their consent;
• Right handed;
• Age > 18 and < 65;
• With a DSM-IV diagnosis of MDD, single episode or recurrent;
• With an antidepressant treatment unchanged in the 3 last weeks;
• With an MADRS score ≥ 21;
• Benzodiazepine treatments have to be avoided;

Exclusion Criteria:

• Major depressive episode with psychotic characteristics;
• A lifetime of the following axis 1 diagnoses: schizophrenia or substance use disorder (alcohol or other substance);
• Stade 5 of Thase and Rush classification ;
• Involuntary hospitalizations;
• Patients under guardianship;
• Outpatients in case of an increased risk of suicide as assessed by a MADRS item 10 > 3;
• Contraindication for MRI or rTMS: a personal history of a seizure disorder, presence of neurologic or neurosurgical disorder, presence of ferromagnetic material (including intraocular) or metallic medical devices (pacemakers);
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Neuronavigation system; 10 sessions of rTMS coupled with a neuronavigation system Description of 1 session of the rTMS protocol : Frequency: 20Hz; Intensity: 110% of motor threshold; 80 train of 2 seconds duration; 10 seconds between two trains; 3200 pulses Devices : rTMS: System Mag Pro (Magventure, Denmark); Neuronavigation system: Syneika One (Syneika, France)	Device: Neuronavigation system; Neuronavigation; Other Names: Syneika One (Syneika, France)
SHAM_COMPARATOR: Standard localisation method; 10 sessions of rTMS with manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method') Description of 1 session of the rTMS protocol : Frequency: 20Hz; Intensity: 110% of motor threshold; 80 train of 2 seconds duration; 10 seconds between two trains; 3200 pulses Devices : - rTMS: System Mag Pro (Magventure, Denmark)	Device: Standard localisation method; Manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	Response defined as at least 50% reduction in the MADRS score.	Day 44

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	Response is defined as at least 50% reduction in the MADRS score.	Day 14
Remission	Remission is defined as a MADRS score ≤ 8.	Day 14 Day 44
MADRS	Description: It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.	Day 0, day 14 and day 44
BDI	It is a multiple-choice self-report inventory and one of the most widely used instruments for measuring the severity of depression.	Day 0 Day 14 Day 14
ERD	It is a 14-item questionnaire which psychiatrists use to measure the intensity of motor retardation.	Day 0 Day 14 day 44

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Bruno Millet, MD PhD, CHU Rennes; Study Chair: Jean Michel Reymann, PhD, CHU Rennes

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 21, 2013
• Primary Completion (ACTUAL): March 25, 2017
• Study Completion (ACTUAL): March 25, 2017

Study Registration Dates

• First Submitted: August 29, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (ESTIMATE): August 31, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: rTMS; Major depressive disorder; Neuronavigation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 2011-A01272-39