Effects of Deep Brain Stimulation in Treatment Resistant Major Depression (FORESEE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Thomas E. Schlaepfer, MD, University Hospital, Bonn
ClinicalTrials.gov Identifier:
NCT01095263
First received: March 24, 2010
Last updated: October 28, 2013
Last verified: October 2013
  Purpose

The investigators will investigate in a sham controlled design antidepressant effects and safety of DBS to the superolateral branch of the main medial forebrain bundle (slMFB).


Condition Intervention Phase
Major Depression
Device: DBS
Device: No Stimulation (Sham)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, 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: 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: 12 month after DBS stimulation onset ] [ Designated as safety issue: No ]

    Change in MADRS after 12 months as compared to mean baseline score. 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.

    MADRS will be rated 3 times for baseline assessment, weekly during parameter optimization and monthly during follow-up. Reduction compared to baseline will be assessed after 12 months of DBS.



Secondary Outcome Measures:
  • Depression Severity rated with Hamilton Depression Rating Scale (HDRS24) [ Time Frame: 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.


  • Adverse Event Schedule [ Time Frame: 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 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. SAEs will be discussed individually if a modification of study protocol is required.

  • Comprehensive neuropsychological test battery [ Time Frame: 12 month after DBS stimulation onset ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: April 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sham then Stimulation Device: DBS
130Hz, 90us pulsewidth, 4V Amplitude
Other Name: INS
Device: No Stimulation (Sham)
130Hz, 90us pulsewidth, 0V Amplitude
Other Name: INS
Experimental: Stimulation then Sham Device: DBS
130Hz, 90us pulsewidth, 4V Amplitude
Other Name: INS
Device: No Stimulation (Sham)
130Hz, 90us pulsewidth, 0V Amplitude
Other Name: INS

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:

MNI152 coordinates:

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

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, MNI152=Montreal Neurologic Institute brain 152 coordinates, MCP = mid-commissural point coordinates, lat. = lateral, ap= antero-posterior, vert. = vertical.

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

In addition to the described intervention, we will record EEG activity within the implanted regions during cognitive paradigms (Fell and Axmacher, Nat Rev Neurosci 2011). Specifically, we will investigate the neural mechanisms underlying classification learning, working memory and exploration of rewarded spatial locations and explore oscillatory responses following stimulation of the target regions. These experimental paradigms will be conducted on the first day after electrode implantation.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Major depression (MD), severe, unipolar type
  • German mother tongue
  • Hamilton Depression Rating Scale (HDRS24) score of > 20
  • Global Assessment of Function (GAF) score of < 45
  • At least 4 episodes of MD or chronic episode > 2 years
  • > 5 years after first episode of MD
  • 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
  • No medical comorbidity
  • Drug free or on stable drug regimen at least 6 weeks before study entry

Exclusion Criteria:

  • Current or past nonaffective 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01095263

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

Additional Information:
Publications:
Responsible Party: Thomas E. Schlaepfer, MD, Professor of Psychiatry and Psychotherapy, University Hospital, Bonn
ClinicalTrials.gov Identifier: NCT01095263     History of Changes
Other Study ID Numbers: BSG-10-4711DBS
Study First Received: March 24, 2010
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 July 20, 2014