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

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)

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).

Study Overview

• Status: Completed
• Conditions: Major Depression
• Intervention / Treatment: Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator

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 Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, 53105
    • University Hospital Bonn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Stimulation for 8 weeks; Implantation of internal pulse generator (IPG), Sham Stimulation	Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator; Device: DBS 130 Hertz (Hz) frequency, 90us pulsewidth, 4 Volt (V) currency Amplitude Device: DBS - No Stimulation (Sham) 130 Hertz (Hz)frequency, 90us pulsewidth, 0 Volt (V) currency Amplitude
Active Comparator: Stimulation for 8 weeks; Implantation of IPG and active stimulation	Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator; Device: DBS 130 Hertz (Hz) frequency, 90us pulsewidth, 4 Volt (V) currency Amplitude Device: DBS - No Stimulation (Sham) 130 Hertz (Hz)frequency, 90us pulsewidth, 0 Volt (V) currency Amplitude

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)	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.	6 and 12 month after DBS stimulation onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)	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.	6 and 12 month after DBS stimulation onset

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive neuropsychological test battery		6 and 12 month after DBS stimulation onset
Adverse Event Schedule	Adverse events will be recorded during the study using a structured questionnaire. All possible adverse events (AEs) are assessed in severity, duration and actions taken. 12 months after stimulation onset results will be compiled and rated as being due to the surgical procedure, device, or stimulation. Serious adverse events (SAEs) will be discussed individually if a modification of study protocol is required. Additional, there will be a safety and efficacy analysis after 6 implanted patients.	6 and 12 month after DBS stimulation onset

Collaborators and Investigators

• Sponsor: University Hospital, Bonn
• Investigators: Principal Investigator: Thomas E. Schlaepfer, MD, University Hospital, Bonn; Principal Investigator: Volker Coenen, MD, University Hospital Freiburg

Publications and helpful links

General Publications

• 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.

Helpful Links

• DBS target site description

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: January 18, 2013
• First Submitted That Met QC Criteria: January 25, 2013
• First Posted (Estimate): January 29, 2013

Study Record Updates

• Last Update Posted (Actual): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: BSG-13-2319DBS