Clinical trial NCT01677078: Coupling Repetitive Transcranial Magnetic Stimulation With a Neuronavigation System in Treatment Resistant Depression
Official title: Assessment of the Neuronavigation System Coupled With Repetitive Transcranial Magnetic Stimulation. A Randomized Double Blind Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Treatment Resistant Depression
Keywords: Major depressive disorder
rTMS
Neuronavigation
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2012-08-31
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Response
timeFrame: Day 44
Secondary outcomes:
measure: Response
timeFrame: Day 14
measure: Remission
timeFrame: Day 14 Day 44
measure: MADRS
timeFrame: Day 0, day 14 and day 44
measure: BDI
timeFrame: Day 0 Day 14 Day 14
measure: ERD
timeFrame: Day 0 Day 14 day 44
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Santé Mentale Angevin CESAME
city: Brest
country: France
facility: CHU de Brest
city: Quimperlé
country: France
facility: Etablissement Public de Santé Mentale
city: Rennes
country: France
facility: CHGR
city: St Avé
country: France
facility: EPSM Morbihan
Study officials:
affiliation: CHU Rennes
name: Bruno Millet, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Rennes
name: Jean Michel Reymann, PhD
role: STUDY_CHAIR
References: