Clinical trial NCT03653858: Efficacy Study of Deep Brain Stimulation in Patients With Treatment Resistant Major Depression
Official title: Controlled Randomized Clinical Trial to Assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients With Treatment Resistant Major Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Treatment-resistant Depression
Keywords: Deep Brain Stimulation
Treatment-resistant depression
Medial forebrain bundle
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2018-08-31
Enrollment: 47
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, randomized, sham-controlled, double blind (patient and observer blinded)
Primary purpose: TREATMENT

Brief summary: The primary objective of this multicenter, randomized, sham-controlled, double blind (patient and observer blinded) clinical trial is to assess the antidepressant effect of Deep Brain Stimulation (DBS) in patients with treatment resistant major depression using the Boston Scientific implantable Vercise™ GEVIA™ DBS system compared to sham.

Detailed description: The main objective of this clinical trial is to assess the putative antidepressant efficacy of a therapeutic method called Deep Brain Stimulation (DBS) in patients suffering from severe, treatment-resistant depression, i.e. in patients who have not sufficiently improved under established antidepressant therapies (such as psychotherapy, antidepressant drug therapy, and electroconvulsive therapy).

DBS, also known as "brain pacemaker" therapy, is a neurosurgical therapeutic method that is widely established for the treatment of other conditions such as Parkinson's disease. However, DBS is not yet approved for the treatment of patients with depression.

In order to initiate DBS treatment, a neurosurgical procedure is performed in which electrodes are placed in a brain region termed 'medial forebrain bundle' (MFB). The electrodes are then used to stimulate this region with electric pulses. From previous investigations and studies with small numbers of patients, it is believed that DBS might have a positive effect on depressive symptoms in patients treated with the method.

Eligibility criteria: Inclusion Criteria:

1. Major depression (MD), severe, unipolar, or bipolar in an acute depression episode.
2. German mother tongue or fluent.
3. Male or female patients ≥20 and ≤75 years.
4. Hamilton Depression Rating Scale (HDRS-28) score of \>21.
5. Global Assessment of Function (GAF) score of \<45.
6. At least 4 episodes of depression or one chronic episode \>2 years.
7. Failure to respond to

   1. adequate trials of primary antidepressants from at least 3 different classes (\>5 weeks at the maximum recommended or tolerated dose) and
   2. adequate trials of augmentation/combination of a primary antidepressant (\>3 weeks at the usually recommended or maximum tolerated dose) using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) and
   3. an adequate trial of electroconvulsive therapy (ECT) (\>6 treatments) and an adequate trial of individual psychotherapy (\>20 sessions with an experienced psychotherapist).
8. Able to give written informed consent.
9. Compliance to participate in the study.
10. Drug free or on stable drug regimen at least 6 weeks before study entry.

Exclusion Criteria:

1. Current or past non-affective psychotic disorder.
2. Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome.
3. Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI), any contraindications to perform a planned MRI to visualize the slMFB.
4. Any surgical contraindications to undergoing DBS like deformed or displaced or not discernable target region, scarring after brain disease (infarction), need for continuous anticoagulation that cannot be bridged in order to obtain normal coagulation, present risks for anesthesia or any brain or scalp injury (even after intracranial surgery).
5. Current or unstably remitted substance abuse (aside from nicotine).
6. Pregnancy, women of childbearing age not using effective contraception and breast feeding women.
7. History of severe personality disorder.
8. Acute suicidal ideation.
9. Patients with advanced stage cardiovascular disease.
10. Patients under immunosuppressive or chemo therapy because of malignant disease.
11. Patients who had previous intracranial surgery.
12. Patients who are currently under DBS therapy or have implanted any kind of stimulator already.
13. Patients with aneurysm clips.
14. Patients with cochlear implants.
15. Patients with planned diathermy.
16. Persons who are in a relationship of dependence/employment with the sponsor or the investigator.
17. Simultaneous participation or previous participation within 30 days prior to start of screening in a clinical trial involving investigational medicinal product(s) or investigational medical device(s).

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS) total score
timeFrame: 16 weeks after surgery
measure: Time to Montgomery-Asberg Depression Rating Scale (MADRS) augmentation of >5 points or clinical worsening in two consecutive visits after DBS termination
timeFrame: Up to 3 months
measure: Assessment of (Serious) Adverse Events related to Investigational Medical Device and / or surgical procedures
timeFrame: From IMD implantation until the end of study; assessed up to 77 weeks
Secondary outcomes:
measure: Hamilton Depression Rating Scale (HDRS-28) total score
timeFrame: 16 weeks after surgery
measure: Clinical Global Impression Score (CGI) total score
timeFrame: 16 weeks after surgery
measure: Global Assessment of Functioning (GAF) total score
timeFrame: 16 weeks after surgery
measure: Beck Depression Inventory (BDI-II) total score
timeFrame: 16 weeks after surgery
measure: 36-Item Short Form Health Survey (SF-36) total score
timeFrame: 16 weeks after surgery
measure: Change over time in HDRS total score after DBS surgery with DB stimulation OFF compared to stimulation ON
timeFrame: assessed weekly for 16 weeks after surgery
measure: Change over time in CGI total score after DBS surgery with DB stimulation OFF compared to stimulation ON
timeFrame: assessed weekly for 16 weeks after surgery
measure: Change over time in GAF total score after DBS surgery with DB stimulation OFF compared to stimulation ON
timeFrame: assessed weekly for 16 weeks after surgery
measure: Change over time in BDI-II total score after DBS surgery with DB stimulation OFF compared to stimulation ON
timeFrame: assessed weekly for 16 weeks after surgery
measure: Change over time in SF-36 total score after DBS surgery with DB stimulation OFF compared to stimulation ON
timeFrame: assessed weekly for 16 weeks after surgery
measure: Neuropsychological Assessments: Rey Complex Figure Test (CFT)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: d2 concentration test (d2)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: 5-Point-Test
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Wechsler Adult Intelligence Scale (WAIS) (vocabulary, similarities)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Mini-Mental-Status-Test (MMST)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Multiple-Choice Vocabulary Intelligence Test (MWT-B)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Rey Visual Design Learning Test (RVDLT)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Word Fluency Test
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Stroop-Test
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Test for Attentional Performance (TAP)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Trail-Making Test (TMT)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Verbal Memory and Learning Ability Test
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Hopper Visual Organization Test (VOT)
timeFrame: at 4 months after implantation
measure: Neuropsychological Assessments: Digit-Span and Block-Span Test
timeFrame: at 4 months after implantation
measure: MADRS total score during long-term follow-up compared to baseline
timeFrame: at 12 months stimulation
measure: HDRS total score during long-term follow-up compared to baseline
timeFrame: at 12 months stimulation
measure: CGI total score
timeFrame: at 6 and 12 months DB stimulation compared to baseline
measure: GAF total score
timeFrame: at 6 and 12 months DB stimulation compared to baseline
measure: BDI-II total score
timeFrame: at 6 and 12 months DB stimulation compared to baseline
measure: SF-36 total score
timeFrame: at 6 and 12 months DB stimulation compared to baseline
measure: Neuropsychological Assessments: Rey Complex Figure Test (CFT)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: d2 concentration test (d2)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: 5-Point-Test
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Wechsler Adult Intelligence Scale (WAIS) (vocabulary, similarities)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Mini-Mental-Status-Test (MMST)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Multiple-Choice Vocabulary Intelligence Test (MWT-B)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Rey Visual Design Learning Test (RVDLT)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Word Fluency Test
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Stroop-Test
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Test for Attentional Performance (TAP)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Trail-Making Test (TMT)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Verbal Memory and Learning Ability Test
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Hopper Visual Organization Test (VOT)
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Neuropsychological Assessments: Digit-Span and Block-Span Test
timeFrame: at 6 months DBS compared to baseline and at end of the study compared to baseline, assessed up to 77 weeks
measure: Incidence of relapse into clinical depression after tapering down of DBS
timeFrame: From discontinuation of DBS until the date of first documented relapse, assessed up to 12 weeks
measure: Pattern of metabolic activity as measured by FDG-PET at 1 week and 4 months after implantation compared to baseline
timeFrame: at 1 week and 4 months after implantation compared to baseline
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Université Grenoble Alpes
city: Freiburg
country: Germany
facility: University Hospital Freiburg
state: Baden-Württemberg
Study officials:
affiliation: University Hospital Freiburg
name: Thomas E Schlaepfer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: