Deep Brain Stimulation (DBS) for Treatment-Resistant Depression (TRD)

July 10, 2019 updated by: Paul Holtzheimer

Deep Brain Stimulation for Treatment-Resistant Depression

In this pilot study, we propose to test whether high frequency stimulation of the subcallosal cingulate (SCC) is a safe and efficacious antidepressant treatment in five TRD patients, to compare the effects of left-sided vs. right-sided stimulation, and to investigate potential mechanisms of action of this intervention. Importantly, this study will be used to assess the need for and assist in planning a larger, more definitive trial of SCC DBS for TRD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The U.S. lifetime prevalence of major depressive disorder (MDD) is 17%. A number of treatments are available for depression including medications, psychotherapy and various somatic treatments. Unfortunately, up to two-thirds of patients remain symptomatic following first-line treatment and a third fail to achieve remission (defined as full resolution of depressive symptoms) after four established treatments; approximately 10%-20% of depressed patients may show virtually no improvement despite multiple, often aggressive treatments. Thus, a conservative estimate places the U.S. prevalence of treatment-resistant depression (TRD) at 1%-3%. TRD has a high risk of suicide, is a major cause of disability and is responsible for doubling of overall health care costs.

For patients with TRD there are limited evidence-based treatment options. Transcranial magnetic stimulation (TMS) may have efficacy for patients that have failed no more than one antidepressant medication 10-12, but response and remission rates are relatively low (under 30% and 20% respectively). Vagus nerve stimulation (VNS) may have efficacy in patients that have failed 4-6 antidepressant treatments but long-term response and remission rates are again low (about 20% and 10% respectively). Electroconvulsive therapy(ECT) can be effective in TRD patients with remission rates of 50%-60%. However, more than 70% of TRD patients will relapse within 6 months following a successful acute treatment course. For patients that have failed ECT, there are no evidence-based treatment options. Therefore, there is great need for novel treatment approaches for TRD.

Prior clinical trials have shown that SCC DBS has the potential to be a valuable treatment option for patients with TRD. Further developing this treatment will involve confirming its effectiveness and identifying ways to optimize its use. In this study we intend to test the safety and efficacy of chronic SCC DBS as a treatment for TRD and compare the safety and efficacy of left-sided versus right-sided stimulation using a double-blind, randomized, cross-over design.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Dartmouth-Hitchcock Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

A partial list of eligibility criteria includes:

  • Age 18-70 years old
  • Ability to provide written informed consent
  • Current Major Depressive Episode (MDE), secondary to either Major Depressive Disorder or Bipolar Disorder (I, II or NOS)
  • A current depressive episode of at least 12 months duration
  • For patients with a bipolar disorder, the last hypomanic or manic episode must have been at least 2 years before study entry
  • A maximum Global Assessment of Functioning of 50
  • Able to tolerate general anesthesia, DBS surgery and MRI scans
  • No significant cerebrovascular risk factors or a previous stroke, documented major head trauma or neurodegenerative disorder
  • No currently active clinically significant Axis I psychiatric diagnosis or a personality disorder likely to interfere with the study
  • No evidence of global cognitive impairment
  • Lives locally or willing to relocate to the area for up to One Year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Left-sided SCC DBS
Active Stimulation of the left-sided electrode
Device: SCC DBS
Deep Brain Stimulator
Other Names:
  • Libra(TM) Implantable Deep Brain Stimulation (DBS) System
Active Comparator: Right-sided SCC DBS
Active stimulation of the right-sided electrode
Device: SCC DBS
Deep Brain Stimulator
Other Names:
  • Libra(TM) Implantable Deep Brain Stimulation (DBS) System

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of 12 Weeks of Left Unilateral DBS vs. 12 Weeks Right Unilateral DBS on Change in 17-item Hamilton Depression Rating Scale (HDRS-17)
Time Frame: baseline, 12 weeks of phase 1, 12 weeks of phase 2 and 12 weeks of phase 3 (bilateral stimulation)
Baseline HDRS-17 is defined as the average of 4 weekly HDRS-17 in the 4 weeks leading up to surgery. Change in HDRS-17 after 12 weeks of left-sided stimulation (compared to baseline) will be compared to change in HDRS-17 after 12 weeks of right-sided stimulation (compared to baseline). The scale ranges from 0-48 with higher scored indicating more severe depression. A cutoff of 7 or below is considered remission from depression. A decrease of at least 50% from baseline is considered an antidepressant response.
baseline, 12 weeks of phase 1, 12 weeks of phase 2 and 12 weeks of phase 3 (bilateral stimulation)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Paul Holtzheimer

Investigators

  • Principal Investigator: Paul E Holtzheimer, MD, Dartmouth-Hitchcock Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2013

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

July 9, 2013

First Submitted That Met QC Criteria

July 9, 2013

First Posted (Estimate)

July 12, 2013

Study Record Updates

Last Update Posted (Actual)

July 25, 2019

Last Update Submitted That Met QC Criteria

July 10, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D12051
  • 23293 (Other Identifier: Dartmouth Committee for the Protection of Human Subjects)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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