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Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression (STHYM)

Primary Purpose

Major Depressive Disorder, Recurrent Depressive Disorder, Bipolar Disorder

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

DBS

SHAM

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major depressive disorder, Recurrent depressive disorder, Bipolar disorder, Deep brain stimulation, Accumbens

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

APHM
APHP Pitié Salpetriere
CHS
CHS
CHU

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

DBS

SHAM

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Response = 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version) (yes/no)

Response is defined as a 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version)

Secondary Outcome Measures

Remission (yes/no)

Remission is defined as an HDRS-17 score < 7

CGI (Clinical global impressions) amelioration (yes/no)

Score of 1 or 2 (item 2 of the CGI)

GAF (Global assessment of functioning)

Presence of a score ≥ 60

HDRS-17 (Hamilton depression rating scale, 17 items version)

Score

MADRS (Montgomery-Asberg Depression Rating Scale)

Score

BDI (Beck Depression Inventory)

Score

CGI (Clinical global impressions)

Score

LARS (Lille Apathy Rating scale)

Score

GAF (Global assessment of functioning)

Score

Neuropsychological assessment

Cerebral metabolism (PET scans)

Adverse events

Adverse events occuring during the study.

Full Information

NCT ID

NCT01973478

First Posted

October 8, 2013

Last Updated

December 26, 2019

Sponsor

Rennes University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01973478

Brief Title

Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

Acronym

STHYM

Official Title

Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

June 3, 2014 (Actual)

Primary Completion Date

July 3, 2017 (Actual)

Study Completion Date

November 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Rennes University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder, Recurrent Depressive Disorder, Bipolar Disorder

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderOutcomes Assessor

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DBS

Arm Type

Experimental

Arm Description

Arm Title

SHAM

Arm Type

Sham Comparator

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

DBS

Intervention Type

Device

Intervention Name(s)

SHAM

Primary Outcome Measure Information:

Title

Response = 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version) (yes/no)

Description

Response is defined as a 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version)

Time Frame

Month 7

Secondary Outcome Measure Information:

Title

Remission (yes/no)

Description

Remission is defined as an HDRS-17 score < 7

Time Frame

Month 7

Title

CGI (Clinical global impressions) amelioration (yes/no)

Description

Score of 1 or 2 (item 2 of the CGI)

Time Frame

Month 7

Title

GAF (Global assessment of functioning)

Description

Presence of a score ≥ 60

Time Frame

Month 7

Title

HDRS-17 (Hamilton depression rating scale, 17 items version)

Description

Score

Time Frame

Month 7

Title

MADRS (Montgomery-Asberg Depression Rating Scale)

Description

Score

Time Frame

Month 7

Title

BDI (Beck Depression Inventory)

Description

Score

Time Frame

Month 7

Title

CGI (Clinical global impressions)

Description

Score

Time Frame

Month 7

Title

LARS (Lille Apathy Rating scale)

Description

Score

Time Frame

Month 7

Title

GAF (Global assessment of functioning)

Description

Score

Time Frame

Month 7

Title

Neuropsychological assessment

Time Frame

Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24

Title

Cerebral metabolism (PET scans)

Time Frame

Day -7; Month 7

Title

Adverse events

Description

Adverse events occuring during the study.

Time Frame

Month 24

Other Pre-specified Outcome Measures:

Title

HDRS-17 (Hamilton depression rating scale, 17 items version)

Description