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

December 26, 2019 updated by: Rennes University Hospital

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Marseille, France
        • APHM
      • Paris, France
        • APHP Pitié Salpétrière
      • Poitiers, France
        • CHS
      • Rouen, France
        • CHS
      • Toulouse, France
        • CHU

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response = 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version) (yes/no)
Time Frame: Month 7
Response is defined as a 50 % decrease of the HDRS-17 (Hamilton depression rating scale, 17 items version)
Month 7

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Remission (yes/no)
Time Frame: Month 7
Remission is defined as an HDRS-17 score < 7
Month 7
CGI (Clinical global impressions) amelioration (yes/no)
Time Frame: Month 7
Score of 1 or 2 (item 2 of the CGI)
Month 7
GAF (Global assessment of functioning)
Time Frame: Month 7
Presence of a score ≥ 60
Month 7
HDRS-17 (Hamilton depression rating scale, 17 items version)
Time Frame: Month 7
Score
Month 7
MADRS (Montgomery-Asberg Depression Rating Scale)
Time Frame: Month 7
Score
Month 7
BDI (Beck Depression Inventory)
Time Frame: Month 7
Score
Month 7
CGI (Clinical global impressions)
Time Frame: Month 7
Score
Month 7
LARS (Lille Apathy Rating scale)
Time Frame: Month 7
Score
Month 7
GAF (Global assessment of functioning)
Time Frame: Month 7
Score
Month 7
Neuropsychological assessment
Time Frame: Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24
Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24
Cerebral metabolism (PET scans)
Time Frame: Day -7; Month 7
Day -7; Month 7
Adverse events
Time Frame: Month 24
Adverse events occuring during the study.
Month 24

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
HDRS-17 (Hamilton depression rating scale, 17 items version)
Time Frame: 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
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
MADRS (Montgomery-Asberg Depression Rating Scale)
Time Frame: 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
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
BDI (Beck Depression Inventory)
Time Frame: 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
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
CGI (Clinical global impressions)
Time Frame: 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
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
LARS (Lille Apathy Rating scale)
Time Frame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Longitudinal evolution of the score
Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
GAF (Global assessment of functioning)
Time Frame: Month -3 ; Month -1; Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Longitudinal evolution of the score
Month -3 ; Month -1; Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
YMRS (Young Mania Rating Scale)
Time Frame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Longitudinal evolution of the score
Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
MATHYS (Multidimensional Assessment of Thymic States)
Time Frame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Longitudinal evolution of the score
Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Response (50 % decrease of the HDRS-17)
Time Frame: Month 24
During the whole follow up
Month 24
Remission
Time Frame: M24
During the whole follow up Remission is defined as an HDRS-17 score < 7
M24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rennes University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jean Michel Reymann, CIC INSERM 0203 CHU Rennes
  • Study Chair: Florian Naudet, CIC INSERM 0203 CHU Rennes
  • Principal Investigator: Bruno Millet, Groupe Hospitalier Pitie-Salpetriere

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 3, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 3, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 27, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 8, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 31, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 27, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 26, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 35RC08_8902

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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