Clinical trial NCT01778790: Deep Brain Stimulation of the Superolateral Branch of the Medial Forebrain Bundle (slMFB) for the Treatment of Refractory Major Depression
Official title: Assessment of Efficacy, Safety and Effects on Quality of Life of Deep Brain Stimulation to the Medial Forebrain Bundle in Patients With Treatment Resistant Major Depression (FORESEE II: FOREbrain Stimulation dEprEssion)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depression
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2013-01-29
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model description: Deep Brain Stimulation
Primary purpose: TREATMENT

Brief summary: The investigators will investigate in a sham controlled staggered onset design antidepressant effects and safety of deep brain stimulation (DBS) to the superolateral branch of the main medial forebrain bundle (slMFB).

Detailed description: The target point for DBS in major depression disorder is located lateral to the ventral tegmental area (VTA) in the midbrain at the branching point of the superolateral branch (slMFB) from the main medial forebrain bundle (MFB).

The exact stimulation coordinates are:

Montreal Neurologic Institute brain 152 coordinates (MNI152 coordinates):

left: x(lat.)=-5, y(ap)=-14, z(vert.)=-8 right: x(lat.)=5, y(ap)=-14, z(vert.)=-9

Mid-commissural point coordinates (MCP coordinates):

eft: x(lat.)=-6, y(ap)=-1, z(vert.)=-6 right: x(lat.)=4, y(ap)=-1, z(vert.)=-7

All coordinates refer to the MNI152 brain.

Legend:

slMFB = superolateral branch of medial forebrain bundle lat. = lateral, ap= anteroposterior, vert. = vertical.

More information can be found at: http://goo.gl/n9sWV

Eligibility criteria: Inclusion Criteria:

* Major depression (MD), severe, unipolar
* German mother tongue
* Age 20 to 75 Years
* Hamilton Depression Rating Scale (HRSD24) score of \> 21
* Global Assessment of Function (GAF) score of \< 45
* At least 4 episodes of depression or chronic episode \> 2 years
* Failure to respond to

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

Exclusion Criteria:

* Current or past non-affective psychotic disorder
* Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome
* Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI)
* Any surgical contraindications to undergoing DBS
* Current or unstably remitted substance abuse (aside from nicotine)
* Pregnancy and women of childbearing age not using effective contraception
* History of severe personality disorder
* Acute suicidal tendency

Primary outcomes:
measure: Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)
timeFrame: 6 and 12 month after DBS stimulation onset
Secondary outcomes:
measure: Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)
timeFrame: 6 and 12 month after DBS stimulation onset
Other outcomes:
measure: Comprehensive neuropsychological test battery
timeFrame: 6 and 12 month after DBS stimulation onset
measure: Adverse Event Schedule
timeFrame: 6 and 12 month after DBS stimulation onset
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn
Study officials:
affiliation: University Hospital, Bonn
name: Thomas E. Schlaepfer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Freiburg
name: Volker Coenen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kilian HM, Meyer DM, Bewernick BH, Spanier S, Coenen VA, Schlaepfer TE. Discontinuation of Superolateral Medial Forebrain Bundle Deep Brain Stimulation for Treatment-Resistant Depression Leads to Critical Relapse. Biol Psychiatry. 2019 Mar 15;85(6):e23-e24. doi: 10.1016/j.biopsych.2018.07.025. Epub 2018 Sep 22. No abstract available.