Deep Brain Stimulation of the Superolateral Branch of the Medial Forebrain Bundle (slMFB) for the Treatment of Refractory Major Depression

Phase 2

Completed

• Conditions: Major Depression
• Interventions: Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator

• Registration Number: NCT01778790
• Lead Sponsor: University Hospital, Bonn

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

Study Timeline

• Study First Submitted: 2013-01-18
• Study First Submitted QC: 2013-01-25
• Study First Posted: 2013-01-29
• Study Start: 2013-07
• Primary Completion: 2016-02
• Study Completion: 2018-01
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-03
• Last Update Posted: 2018-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Sham Stimulation for 8 weeks	Deep Brain Stimulation with Activa PC Multi-program Neurostimulator	Implantation of internal pulse generator (IPG), Sham Stimulation
Stimulation for 8 weeks	Deep Brain Stimulation with Activa PC Multi-program Neurostimulator	Implantation of IPG and active stimulation

Primary Outcome Measures

Name	Time	Method
Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)	6 and 12 month after DBS stimulation onset	Change in MADRS after 6 and 12 months as compared to mean baseline score and one month placebo treatment. MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. It is used as an adjunct to the Hamilton Rating Scale for Depression (HAMD) and more sensitive to the changes in depression than the Hamilton Scale is.

Secondary Outcome Measures

Name	Time	Method
Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)	6 and 12 month after DBS stimulation onset	The Hamilton Rating Scale for Depression (HRSD), also known as the Hamilton Depression Rating Scale (HDRS) or abbreviated to HAM-D, is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. The questionnaire rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight loss. The questionnaire is presently one of the most commonly used scales for rating depression in medical research.; Measures will be taken at same time points as primary outcome measure.

Trial Locations

Locations (1)

University Hospital Bonn; 🇩🇪 Bonn, Germany