Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

NCT ID: NCT01973478

Last Updated: 2019-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-03

Study Completion Date

2018-11-27

Brief Summary

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Major depressive disorders are real public health issues in terms of diagnosis and treatment. Some forms of depression are chronic and resistant to treatment (TRD). In these forms suicide risk is important.

Patients with TRD are potential candidates for neurosurgical interventions to treat depression. However, psychosurgery interventions based upon lesions, showed their limitations related to 1. the large variability in neurosurgical gestures, 2. their side effects, and of course 3. the irreversible damage caused by the surgery.

Thus, deep brain stimulation (DBS) could represent an opportunity for patients suffering from TRD. Our preliminary study based upon the stimulation of the accumbens nucleus showed encouraging results. The investigators have thus planned a randomized controlled trial versus sham stimulation to confirm the therapeutic value of nucleus accumbens DBS.

Detailed Description

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Because of their recurrent nature, their prevalence and their consequences, major depressive disorders are real public health issues in terms of diagnosis and treatment.

Some forms of depression are chronic and resistant to treatment (TRD), either unipolar (repeated episodes of depression) or bipolar (repeated episodes of depression and manic and/or hypomanic episodes). In these forms suicide risk is important.

Patients with TRD are potential candidates for neurosurgical interventions to treat depression. The benefit of neurosurgical procedures is expected to be important in these patients.

Psychosurgery interventions based upon lesions, however, showed their limitations related to 1/ the large variability in neurosurgical gestures, 2/ their side effects, and of course 3/ the irreversible damage caused by the surgery.

Current brain imaging data yielded fresh information about the pathophysiology of depression and suggested new therapeutic approaches in TRD.

Modulation of sub-caudate specific pathways, which are part of orbitofrontal and anterior cingulate cortico-subcortical loops should allow for a diminution of depressive symptoms.

The modulation of these specific pathways, initially targeted by classical neurosurgery, could benefit from current developments in functional neurosurgery.

Deep brain stimulation (DBS) may represent an opportunity for patients suffering from TRD. Our preliminary study based upon the stimulation of the accumbens nucleus showed encouraging results. The investigators have thus planned a randomized controlled trial versus sham stimulation to confirm the therapeutic value of nucleus accumbens DBS.

Conditions

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Major Depressive Disorder Recurrent Depressive Disorder Bipolar Disorder

Keywords

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Major depressive disorder Recurrent depressive disorder Bipolar disorder Deep brain stimulation Accumbens

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors

Study Groups

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DBS

The medical device includes:

* Either a pacemaker ACTIVA PC (Ref 37601) two-channel (Medtronic USA) or two pacemakers Activa SC (Ref 37603) to a channel (Medtronic USA)
* Two DBS electrodes with four contacts (type Medtronic DBS 3389). Patients will be operated with the usual stereotactic surgical procedure.

The target is the Accumbens nucleus.

The two electrodes are implanted in a single session under local anaesthesia or intermittent sedation (propofol parenteral without intubation early intervention). Day 0 is defined by the surgery.

The DBS is "on" during 6 months (between Month 1 and Month 7). Stimulation will also be on after Month 7.

Group Type EXPERIMENTAL

DBS

Intervention Type DEVICE

SHAM

The medical device includes:

* Either a pacemaker ACTIVA PC (Ref 37601) two-channel (Medtronic USA) or two pacemakers Activa SC (Ref 37603) to a channel (Medtronic USA)
* Two DBS electrodes with four contacts (type Medtronic DBS 3389). Patients will be operated with the usual stereotactic surgical procedure.

The target is the Accumbens nucleus.

The two electrodes are implanted in a single session under local anaesthesia or intermittent sedation (propofol parenteral without intubation early intervention). Day 0 is defined by the surgery.

The DBS is "off" during 6 months (between Month 1 and Month 7). Possibility to active the stimulation after Month 7.

Group Type SHAM_COMPARATOR

SHAM

Intervention Type DEVICE

Interventions

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DBS

Intervention Type DEVICE

SHAM

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Age between 18 and 70 years
* DSM-IV (DSM = Diagnostic and Statistical Manual) criteria for a recurrent depressive disorder or bipolar disorder
* Duration of the episode \> 2 years
* Severity of the episode attested by :

* A HDRS score \> 21
* A CGI score ≥ 4
* A GAF \< 50
* Persistence of severity criteria during the screening
* Following characteristics resistance in case of recurrent depressive disorder :

* Stage V of the classification of Thase and Rush
* Unsuccessful treatment by the association of two antidepressants (or intolerance/contra-indications)
* Unsuccessful treatment by the association for at least 6 weeks of one of the following treatments : lithium , thyroid hormone , buspirone , pindolol with an antidepressant (or intolerance/contra-indications)
* Unsuccessful treatment by the combination of a second-generation antipsychotic (olanzapine, risperidone, amisulpride, aripiprazole, clozapine and quetiapine) to an antidepressant (or intolerance/contra-indications)
* Unsuccessful treatment by a structured psychotherapy
* Following characteristics of resistance in case of bipolar disorder:

* Unsuccessful treatment by lithium (or intolerance/contra-indications)
* Unsuccessful treatment by at least one mood stabilizer anticonvulsant (or intolerance/contra-indications)
* Unsuccessful treatment by at least one second-generation antipsychotic (or intolerance/contra-indications)
* Unsuccessful treatment by the combination of two mood stabilizers with at least an anticonvulsant (or intolerance/contra-indications)
* Unsuccessful treatment by electro-convulsive therapy sessions (or intolerance/contra-indications)
* Unsuccessful treatment by at least one antidepressant , mood stabilizer combination (or intolerance/contra-indications)
* Unsuccessful treatment by a structured psychotherapy
* Understanding the conduct of the study
* Giving a written informed consent
* Benefiting from the french social insurance


* Comorbid axis 1 disorder (except dysthymia, generalized anxiety disorder, social phobia, panic disorder)
* Alcohol or other psychoactive substances dependence (except nicotine)
* Suicidal risk during the last month assessed by the MINI (Mini International Neuropsychiatric Interview), the DIGS (Diagnostic Interview for Genetic Studies) and the item 3 of the HDRS
* Suicide attempt in the last 6 months or two suicide attempts in the previous two years
* History of forensic act or furious mania
* Depressive episode with congruent or incongruent psychotic features or history of a depressive episode with psychotic features
* Comorbid cluster A or B personality disorders according to the DSM IV-TR evaluated using the SCID2 (Structured Clinical Interview for DSM-IV)
* Cognitive Impairment (Mattis \< 130)
* MRI (Magnetic Resonance Imaging) contraindication to stimulation or contraindications for MRI
* Major somatic disease making it impossible to set up the study treatment
* Pregnant women, or nursing or childbearing potential without effective contraception
* Involuntary commitment
* Guardianship
* Participation in another study
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rennes University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean Michel Reymann

Role: STUDY_CHAIR

CIC INSERM 0203 CHU Rennes

Florian Naudet

Role: STUDY_CHAIR

CIC INSERM 0203 CHU Rennes

Bruno Millet

Role: PRINCIPAL_INVESTIGATOR

Groupe Hospitalier Pitié-Salpêtrière

Locations

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APHM

Marseille, , France

Site Status

APHP Pitié Salpetriere

Paris, , France

Site Status

CHS

Poitiers, , France

Site Status

CHS

Rouen, , France

Site Status

CHU

Toulouse, , France

Site Status

Countries

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France

Other Identifiers

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35RC08_8902

Identifier Type: -

Identifier Source: org_study_id