STHYM: Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

Sponsor

Rennes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01973478

Collaborator

(none)

Enrollment

Locations

Arms

53.8

Actual Duration (Months)

1.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder Recurrent Depressive Disorder Bipolar Disorder	Device: DBS Device: SHAM	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

Actual Study Start Date :

Jun 3, 2014

Actual Primary Completion Date :

Jul 3, 2017

Actual Study Completion Date :

Nov 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Device: DBS
Sham Comparator: 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.	Device: SHAM

Arm

Intervention/Treatment

Experimental: 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.

Device: DBS

Sham Comparator: 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.

Device: SHAM

Outcome Measures

Primary Outcome Measures

Response = 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version) (yes/no) [Month 7]
Response is defined as a 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version)

Secondary Outcome Measures

Remission (yes/no) [Month 7]
Remission is defined as an HDRS-17 score < 7
CGI (Clinical global impressions) amelioration (yes/no) [Month 7]
Score of 1 or 2 (item 2 of the CGI)
GAF (Global assessment of functioning) [Month 7]
Presence of a score ≥ 60
HDRS-17 (Hamilton depression rating scale, 17 items version) [Month 7]
Score
MADRS (Montgomery-Asberg Depression Rating Scale) [Month 7]
Score
BDI (Beck Depression Inventory) [Month 7]
Score
CGI (Clinical global impressions) [Month 7]
Score
LARS (Lille Apathy Rating scale) [Month 7]
Score
GAF (Global assessment of functioning) [Month 7]
Score
Neuropsychological assessment [Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24]
Cerebral metabolism (PET scans) [Day -7; Month 7]
Adverse events [Month 24]
Adverse events occuring during the study.

Other Outcome Measures

HDRS-17 (Hamilton depression rating scale, 17 items version) [Month -3 ; Month -1; Day -7; Day 15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24]
Longitudinal evolution of the score
MADRS (Montgomery-Asberg Depression Rating Scale) [Month -3 ; Month -1; Day -7; Day 15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24]
Longitudinal evolution of the score
BDI (Beck Depression Inventory) [Day -7; Day 15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24]
Longitudinal evolution of the score
CGI (Clinical global impressions) [Month -3 ; Month -1; Day-7; Day15; Month 1; Day 45; Month 2 ; Day 75 ; Month 3; Month 4; Month 5; Month 6; Month 7; Month 8; Month 9; Month 10; Month 13; Month 16; Month 19; Month 22; Month 24]
Longitudinal evolution of the score
LARS (Lille Apathy Rating scale) [Day -7; Month 1; Month 7; Month 13; Month 19; Month 24]
Longitudinal evolution of the score
GAF (Global assessment of functioning) [Month -3 ; Month -1; Day -7; Month 1; Month 7; Month 13; Month 19; Month 24]
Longitudinal evolution of the score
YMRS (Young Mania Rating Scale) [Day -7; Month 1; Month 7; Month 13; Month 19; Month 24]
Longitudinal evolution of the score
MATHYS (Multidimensional Assessment of Thymic States) [Day -7; Month 1; Month 7; Month 13; Month 19; Month 24]
Longitudinal evolution of the score
Response (50 % decrease of the HDRS-17) [Month 24]
During the whole follow up
Remission [M24]
During the whole follow up Remission is defined as an HDRS-17 score < 7

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Non-Inclusion Criteria:

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