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

Primary Purpose

Major Depression

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Deep Brain Stimulation with Activa PC Multi-program Neurostimulator

About this trial

This is an interventional treatment trial for Major Depression

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University Hospital Bonn

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Active Comparator

Arm Label

Sham Stimulation for 8 weeks

Stimulation for 8 weeks

Arm Description

Implantation of internal pulse generator (IPG), Sham Stimulation

Implantation of IPG and active stimulation

Outcomes

Primary Outcome Measures

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.

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.

Full Information

NCT ID

NCT01778790

First Posted

January 18, 2013

Last Updated

August 3, 2018

Sponsor

University Hospital, Bonn

1. Study Identification

Unique Protocol Identification Number

NCT01778790

Brief Title

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

Acronym

FORESEEII

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

July 2013 (Actual)

Primary Completion Date

February 2016 (Actual)

Study Completion Date

January 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Bonn

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

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 2

Model Description

Deep Brain Stimulation

Masking

ParticipantOutcomes Assessor

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sham Stimulation for 8 weeks

Arm Type

Sham Comparator

Arm Description

Implantation of internal pulse generator (IPG), Sham Stimulation

Arm Title

Stimulation for 8 weeks

Arm Type

Active Comparator

Arm Description

Implantation of IPG and active stimulation

Intervention Type

Device

Intervention Name(s)

Deep Brain Stimulation with Activa PC Multi-program Neurostimulator

Intervention Description

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

Primary Outcome Measure Information:

Title

Depression Severity assessed with Montgomery Asberg Depression Scale (MADRS)

Description

Time Frame

6 and 12 month after DBS stimulation onset

Secondary Outcome Measure Information:

Title

Depression Severity rated with Hamilton Depression Rating Scale (HDRS24)

Description

Time Frame

6 and 12 month after DBS stimulation onset

Other Pre-specified Outcome Measures:

Title

Comprehensive neuropsychological test battery

Time Frame

6 and 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 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.

Time Frame

6 and 12 month after DBS stimulation onset

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas E. Schlaepfer, MD

Organizational Affiliation

University Hospital, Bonn

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Volker Coenen, MD

Organizational Affiliation

University Hospital Freiburg

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

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

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

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