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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01898429
Recruitment Status : Completed
First Posted : July 12, 2013
Results First Posted : September 12, 2018
Last Update Posted : July 25, 2019
Information provided by (Responsible Party):
Paul Holtzheimer, Dartmouth-Hitchcock Medical Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Treatment Resistant Depression Depressive Disorder, Treatment-Resistant Depression, Bipolar Device: SCC DBS Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Deep Brain Stimulation for Treatment-Resistant Depression
Study Start Date : July 2013
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Left-sided SCC DBS
Active Stimulation of the left-sided electrode
Device: SCC DBS
Deep Brain Stimulator
Other Name: 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 Name: Libra(TM) Implantable Deep Brain Stimulation (DBS) System

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   22 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01898429

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United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Paul Holtzheimer
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Principal Investigator: Paul E Holtzheimer, MD Dartmouth-Hitchcock Medical Center

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Responsible Party: Paul Holtzheimer, Deputy Director for Research at the National Center for PTSD, Associate Professor for Dartmouth/Dartmouth Hitchcock., Dartmouth-Hitchcock Medical Center Identifier: NCT01898429     History of Changes
Other Study ID Numbers: D12051
23293 ( Other Identifier: Dartmouth Committee for the Protection of Human Subjects )
First Posted: July 12, 2013    Key Record Dates
Results First Posted: September 12, 2018
Last Update Posted: July 25, 2019
Last Verified: July 2019
Keywords provided by Paul Holtzheimer, Dartmouth-Hitchcock Medical Center:
Treatment Resistant Depression
Treatment Refractory Depression
Treatment Resistant Bipolar Disorder
Treatment Refractory Bipolar Disorder
Deep brain stimulation
Additional relevant MeSH terms:
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Depressive Disorder
Depressive Disorder, Treatment-Resistant
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders