Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

Major Depressive Disorder Clinical Trial

— STHYM  

Official title:

Deep Brain Stimulation in Patients With Chronic Treatment Resistant Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01973478
• Other study ID #: 35RC08_8902
• Status: Completed
• Phase: N/A
• Start date: June 3, 2014
• Est. completion date: November 27, 2018

Study information

• Verified date: December 2019
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: November 27, 2018
• Est. primary completion date: July 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Disease
• Major Depressive Disorder
• Recurrent Depressive Disorder

Intervention

Device:
• DBS

• SHAM

Locations

Country	Name	City	State
France	APHM	Marseille
France	APHP Pitié Salpetriere	Paris
France	CHS	Poitiers
France	CHS	Rouen
France	CHU	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HDRS-17 (Hamilton depression rating scale, 17 items version)	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
Other	MADRS (Montgomery-Asberg Depression Rating Scale)	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
Other	BDI (Beck Depression Inventory)	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
Other	CGI (Clinical global impressions)	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
Other	LARS (Lille Apathy Rating scale)	Longitudinal evolution of the score	Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Other	GAF (Global assessment of functioning)	Longitudinal evolution of the score	Month -3 ; Month -1; Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Other	YMRS (Young Mania Rating Scale)	Longitudinal evolution of the score	Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Other	MATHYS (Multidimensional Assessment of Thymic States)	Longitudinal evolution of the score	Day -7; Month 1; Month 7; Month 13; Month 19; Month 24
Other	Response (50 % decrease of the HDRS-17)	During the whole follow up	Month 24
Other	Remission	During the whole follow up Remission is defined as an HDRS-17 score < 7	M24
Primary	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)	Month 7
Secondary	Remission (yes/no)	Remission is defined as an HDRS-17 score < 7	Month 7
Secondary	CGI (Clinical global impressions) amelioration (yes/no)	Score of 1 or 2 (item 2 of the CGI)	Month 7
Secondary	GAF (Global assessment of functioning)	Presence of a score = 60	Month 7
Secondary	HDRS-17 (Hamilton depression rating scale, 17 items version)	Score	Month 7
Secondary	MADRS (Montgomery-Asberg Depression Rating Scale)	Score	Month 7
Secondary	BDI (Beck Depression Inventory)	Score	Month 7
Secondary	CGI (Clinical global impressions)	Score	Month 7
Secondary	LARS (Lille Apathy Rating scale)	Score	Month 7
Secondary	GAF (Global assessment of functioning)	Score	Month 7
Secondary	Neuropsychological assessment		Day -7 ; Month 1; Month 7; Month 13; Month 19; Month 24
Secondary	Cerebral metabolism (PET scans)		Day -7; Month 7
Secondary	Adverse events	Adverse events occuring during the study.	Month 24