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

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ClinicalTrials.gov Identifier: NCT01973478
Recruitment Status : Suspended (inclusions suspended - new evaluation of benefit/risk ratio)
First Posted : October 31, 2013
Last Update Posted : December 20, 2018
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

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 Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 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 : June 3, 2014
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. Remission (yes/no) [ Time Frame: Month 7 ]
    Remission is defined as an HDRS-17 score < 7

  2. CGI (Clinical global impressions) amelioration (yes/no) [ Time Frame: Month 7 ]
    Score of 1 or 2 (item 2 of the CGI)

  3. GAF (Global assessment of functioning) [ Time Frame: Month 7 ]
    Presence of a score ≥ 60

  4. HDRS-17 (Hamilton depression rating scale, 17 items version) [ Time Frame: Month 7 ]
    Score

  5. MADRS (Montgomery-Asberg Depression Rating Scale) [ Time Frame: Month 7 ]
    Score

  6. BDI (Beck Depression Inventory) [ Time Frame: Month 7 ]
    Score

  7. CGI (Clinical global impressions) [ Time Frame: Month 7 ]
    Score

  8. LARS (Lille Apathy Rating scale) [ Time Frame: Month 7 ]
    Score

  9. GAF (Global assessment of functioning) [ Time Frame: Month 7 ]
    Score

  10. Neuropsychological assessment [ Time Frame: Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24 ]
  11. Cerebral metabolism (PET scans) [ Time Frame: Day -7; Month 7 ]
  12. Adverse events [ Time Frame: Month 24 ]
    Adverse events occuring during the study.


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. 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

  5. LARS (Lille Apathy Rating scale) [ Time Frame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24 ]
    Longitudinal evolution of the score

  6. 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

  7. YMRS (Young Mania Rating Scale) [ Time Frame: Day -7; Month 1; Month 7; Month 13; Month 19; Month 24 ]
    Longitudinal evolution of the score

  8. 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

  9. Response (50 % decrease of the HDRS-17) [ Time Frame: Month 24 ]
    During the whole follow up

  10. Remission [ Time Frame: M24 ]
    During the whole follow up Remission is defined as an HDRS-17 score < 7



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01973478


Locations
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France
CHU
Bordeaux, France
CHU
Clermont Ferrand, France
CHU
Grenoble, France
CHU
Lille, France
CH Le Vinatier
Lyon, France
APHM
Marseille, France
CHU
Nancy, France
CHU
Nantes, France
CHU
Nice, France
APHP Pitié Salpetriere
Paris, France
CH Sainte Anne
Paris, France
CHS
Poitiers, France
CHGR
Rennes, France
CHS
Rouen, France
CHU
Toulouse, France
Sponsors and Collaborators
Rennes University Hospital
Investigators
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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 Pitié-Salpêtrière

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Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01973478     History of Changes
Other Study ID Numbers: 35RC08_8902
First Posted: October 31, 2013    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018

Keywords provided by Rennes University Hospital:
Major depressive disorder
Recurrent depressive disorder
Bipolar disorder
Deep brain stimulation
Accumbens

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Disease
Bipolar Disorder
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders