Efficacy Study of Deep Brain Stimulation in Patients With Treatment Resistant Major Depression (FORESEE III)

University Hospital Freiburg

Status: Enrolling

Conditions: Treatment-resistant Depression

Treatments: Device: Vercise GEVIA deep brain stimulation (DBS) system

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03653858

DRKS00014947 (Registry Identifier)

CIV-17-07-020746 (Other Identifier)

P000767

Details and patient eligibility

About

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.

Full 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.

Enrollment: 47 estimated patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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47 participants in 2 patient groups

Group A: DBS onset in week 1

Experimental group

Description:

Implantation of Vercise GEVIA deep brain stimulation (DBS) system. DBS onset in week 1. 2ND STAGE: After 6 months DBS ON, patients will be assessed whether they are responders or non-responders. In the subgroup of eligible responders, patients will be randomized to either DBS OFF\* (for max. 3 months) or continued DBS for another 6 months. \*DBS OFF until worsening of clinical depression, event (defined as \> 5 points augmentation in MADRS in two consecutive visits) or for a maximum of 3 months. After DBS OFF, re-onset of DBS will be performed, followed by 6 months continuous DBS. Non-responders will also receive another 6 months DBS therapy in the 2nd stage. At sites other than Freiburg/Bonn, the 2nd stage consists of 6 months DBS therapy only.

Treatment:

Device: Vercise GEVIA deep brain stimulation (DBS) system

Group B: DBS off, followed by DBS onset in week 17

Sham Comparator group

Description:

Implantation of Vercise GEVIA deep brain stimulation (DBS) system. 4 months OFF after implantation followed by DBS onset in first week of month 5. 2ND STAGE: See group A.

Treatment:

Device: Vercise GEVIA deep brain stimulation (DBS) system