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

This study is currently recruiting participants.
Verified October 2013 by University Hospital, Bonn
Sponsor:
Information provided by (Responsible Party):
Thomas E. Schlaepfer, MD, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT01778790
First received: January 18, 2013
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

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).


Condition Intervention Phase
Major Depression
Device: Deep Brain Stimulation with Activa PC Multi-program Neurostimulator
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University Hospital, Bonn:

Primary Outcome Measures:
  • Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS) [ Time Frame: 6 and 12 month after DBS stimulation onset ] [ Designated as safety issue: No ]
    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:
  • Depression Severity rated with Hamilton Depression Rating Scale (HDRS24) [ Time Frame: 6 and 12 month after DBS stimulation onset ] [ Designated as safety issue: No ]

    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.



Other Outcome Measures:
  • Comprehensive neuropsychological test battery [ Time Frame: 6 and 12 month after DBS stimulation onset ] [ Designated as safety issue: Yes ]
  • Adverse Event Schedule [ Time Frame: 6 and 12 month after DBS stimulation onset ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 12
Study Start Date: August 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01778790

Contacts
Contact: Sabrina Gippert, BA Sabrina.Gippert@ukb.uni-bonn.de
Contact: Sarah Kayser, MD Sarah.Kayser@ukb.uni-bonn.de

Locations
Germany
University Hospital Bonn Recruiting
Bonn, Germany, 53105
Sponsors and Collaborators
University Hospital, Bonn
Investigators
Principal Investigator: Thomas E. Schlaepfer, MD University Hospital, Bonn
Principal Investigator: Volker Coenen, MD University Hospital Freiburg
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas E. Schlaepfer, MD, Professor of Psychiatry and Psychotherapy, University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT01778790     History of Changes
Other Study ID Numbers: BSG-13-2319DBS
Study First Received: January 18, 2013
Last Updated: October 28, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on April 15, 2014