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

Primary Purpose

Major Depression

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
DBS
No Stimulation (Sham)
Sponsored by
University Hospital, Bonn
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depression

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital Bonn

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sham then Stimulation

Stimulation then Sham

Arm Description

Outcomes

Primary Outcome Measures

Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)
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)
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
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

Full Information

First Posted
March 24, 2010
Last Updated
August 3, 2018
Sponsor
University Hospital, Bonn
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1. Study Identification

Unique Protocol Identification Number
NCT01095263
Brief Title
Effects of Deep Brain Stimulation in Treatment Resistant Major Depression
Acronym
FORESEE
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
April 2011 (Actual)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Bonn

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sham then Stimulation
Arm Type
Experimental
Arm Title
Stimulation then Sham
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
DBS
Other Intervention Name(s)
INS
Intervention Description
130Hz, 90us pulsewidth, 4V Amplitude
Intervention Type
Device
Intervention Name(s)
No Stimulation (Sham)
Other Intervention Name(s)
INS
Intervention Description
130Hz, 90us pulsewidth, 0V Amplitude
Primary Outcome Measure Information:
Title
Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)
Description
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.
Time Frame
12 month after DBS stimulation onset
Secondary Outcome Measure Information:
Title
Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)
Description
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.
Time Frame
12 month after DBS stimulation onset
Title
Adverse Event Schedule
Description
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.
Time Frame
12 month after DBS stimulation onset
Title
Comprehensive neuropsychological test battery
Time Frame
12 month after DBS stimulation onset

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Volker Coenen, MD
Organizational Affiliation
University Hospital, Bonn
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas E. Schlaepfer, MD
Organizational Affiliation
University Hospital, Bonn
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Bonn
City
Bonn
ZIP/Postal Code
53105
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
23206684
Citation
Coenen VA, Schlaepfer TE, Allert N, Madler B. Diffusion tensor imaging and neuromodulation: DTI as key technology for deep brain stimulation. Int Rev Neurobiol. 2012;107:207-34. doi: 10.1016/B978-0-12-404706-8.00011-5.
Results Reference
background
PubMed Identifier
21184778
Citation
Coenen VA, Schlaepfer TE, Maedler B, Panksepp J. Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans. Neurosci Biobehav Rev. 2011 Oct;35(9):1971-81. doi: 10.1016/j.neubiorev.2010.12.009. Epub 2010 Dec 22.
Results Reference
background
PubMed Identifier
23562618
Citation
Schlaepfer TE, Bewernick BH, Kayser S, Madler B, Coenen VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry. 2013 Jun 15;73(12):1204-12. doi: 10.1016/j.biopsych.2013.01.034. Epub 2013 Apr 3.
Results Reference
result
PubMed Identifier
23916389
Citation
Coenen VA, Madler B, Schlaepfer TE. Reply to: medial forebrain bundle stimulation-speed access to an old or entry into a new depression neurocircuit? Biol Psychiatry. 2013 Dec 15;74(12):e45-6. doi: 10.1016/j.biopsych.2013.06.017. Epub 2013 Aug 2. No abstract available.
Results Reference
result
PubMed Identifier
30253883
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.
Results Reference
derived
Links:
URL
http://tiny.cc/sl-mfb
Description
DBS target site description

Learn more about this trial

Effects of Deep Brain Stimulation in Treatment Resistant Major Depression

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