Trial document




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  DRKS00014947

Trial Description

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Title

Controlled Randomized Clinical Trial to assess Efficacy of Deep Brain Stimulation (DBS) of the slMFB in Patients with Treatment Resistant Major Depression

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Trial Acronym

FORESEE III

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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

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Organizational Data

  •   DRKS00014947
  •   2018/08/06
  •   2018/08/31
  •   yes
  •   Approved
  •   382/17, Ethik-Kommission der Albert-Ludwigs-Universität Freiburg
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Secondary IDs

  •   NCT03653858  (clinicaltrials.gov)
  •   CIV-17-07-020746 
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Health Condition or Problem studied

  •   F33.2 -  Recurrent depressive disorder, current episode severe without psychotic symptoms
  •   F33.3 -  Recurrent depressive disorder, current episode severe with psychotic symptoms
  •   F33.8 -  Other recurrent depressive disorders
  •   F33.9 -  Recurrent depressive disorder, unspecified
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Interventions/Observational Groups

  •   ALL PATIENTS:
    Implantation of Vercise™ GEVIATM deep brain stimulation (DBS) system. “Bioelectric activity” testing in a sub-group of 6 patients.

    RANDOMIZED STIMULATION ONSET:
    Group A: 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 at a ratio of 2:1 to either DBS OFF (for max. 3 months) or continued DBS without interruption (for another 6 months). That is, when randomized accordingly, DBS will be turned OFF until worsening of clinical depression or until event (defined as more than 5 points augmentation in MADRS in two consecutive visits). When an event or a relapse occurs after DBS OFF, re-onset of DBS will be performed. In this case, patients will be unblinded and will also receive continuous DBS for a period of 6 months. If no event or relapse occurs, re-onset of DBS will be performed after 3 months, as well followed by 6 months continuous DBS, and blinding will be maintained.
    An interruption of DBS will first be performed in 6 patients only, for three months maximum per patient. In case of feasibility and safety, DBS will be interrupted in more patients.
    Non-responders will also receive another 6 months DBS therapy in the 2nd stage. Blinding will be maintained.
    At sites other than Freiburg/Bonn, the 2nd stage consists of 6 months DBS therapy only. Responder assessment and DBS termination will not be performed at these sites, and patients and raters will be unblinded 6 months after implantation.


  •   ALL PATIENTS:
    Implantation of Vercise™ GEVIATM deep brain stimulation (DBS) system. “Bioelectric activity” testing in a sub-group of 6 patients.

    RANDOMIZED STIMULATION ONSET:
    Group B: 4 months OFF after implantation followed by DBS onset in first week of month 5.

    2ND STAGE: See group A.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, assessor
  •   Placebo
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Primary endpoint (Efficacy):
MADRS at 16 weeks after surgery

Primary endpoint (2nd stage):
Time to MADRS augmentation of >5 points or clinical worsening in two consecutive visits after DBS termination

Primary endpoint (safety):
Assessment of (Serious) Adverse Events related to Investigational Medical Device and / or surgical procedures

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Secondary Outcome

After randomized step:
a)HDRS, CGI, GAF, BDI-II, SF-36 at 16 weeks after surgery.
b)Change over time in HDRS, CGI, GAF, BDI-II, SF-36 after DBS surgery with DB stimulation OFF compared to stimulation ON.
c)Scores in neuropsychological tests (sham vs. DBS) at 4 months.
In whole population after 6 months stimulation:
d)MADRS / HDRS during long-term follow-up (at 6 months open stimulation) compared to baseline.
e)Scores in CGI, GAF, BDI-II, SF-36 at 6 and 12 months DBS compared to baseline.
f)Scores in neuropsychological tests at 6 months DBS compared to baseline and at end of the study compared to baseline.
g)Incidence of relapse into clinical depression after tapering down of DBS.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2018/09/06
  •   47
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   20   Years
  •   75   Years
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Additional Inclusion Criteria

Patients eligible for inclusion in this trial must meet all of the following 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
a.adequate trials of primary antidepressants from at least 3 different classes (>5 weeks at the maximum recommended or tolerated dose) and
b.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
c.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.

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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).

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Addresses

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    • Universitätsklinikum Freiburg
    • Breisacher Str. 153
    • 79110  Freiburg
    • Germany
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    • Universitätsklinikum FreiburgKlinik für Psychiatrie und PsychotherapieAbteilung für Interventionelle Biologische Psychiatrie
    • Mr.  Prof. Dr.  Thomas  Schläpfer 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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    • Universitätsklinikum FreiburgKlinik für Psychiatrie und PsychotherapieAbteilung für Interventionelle Biologische Psychiatrie
    • Mr.  Prof. Dr.  Thomas  Schläpfer 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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Sources of Monetary or Material Support

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    • Boston Scientific Group plc
    • Vestastraat 6
    • 6468  EX Kerkrade
    • Netherlands
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    • Universitätsklinikum FreiburgKlinik für Psychiatrie und PsychotherapieAbteilung für Interventionelle Biologische Psychiatrie
    • Mr.  Prof. Dr.  Thomas  Schläpfer 
    • Hauptstr. 5
    • 79104  Freiburg
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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