Clinical trial NCT03360942: Long Term Follow-up of Deep Brain Stimulation for Treatment-Resistant Depression
Official title: Long Term Follow-up of Deep Brain Stimulation for Treatment-Resistant Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Treatment Resistant Depression
Depressive Disorder, Treatment-Resistant
Depression, Bipolar
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2017-12-04
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The long term follow up of a pilot study in which the investigators proposed 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 Deep Brain Stimulation (DBS) for treatment-resistant depression (TRD).

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 the investigators 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.

Eligibility criteria: Inclusion Criteria:

* Have received DBS for TRD
* Ability to provide written informed consent
* Willing to comply with all necessary study visits

Exclusion Criteria:

* Significant cerebrovascular risk factors or a previous stroke, documented major head trauma or neurodegenerative disorder.
* Other currently active clinically significant Axis I psychiatric diagnosis including schizophrenia, panic disorder, obsessive-compulsive disorder, generalized anxiety disorder or post-traumatic stress disorder. Patients with severe Axis II personality disorders will also be excluded if the personality disorder is likely to interfere with cooperation and adherence to the study protocol.
* Current psychotic symptoms.
* Evidence of global cognitive impairment.
* Substance abuse or dependence not in full sustained remission (i.e., not active for at least one year).
* Active suicidal ideation with intent; suicide attempt within the last six months; more than three suicide attempts within the last two years.
* Pregnancy or plan to become pregnant during the study period.
* General contraindications for DBS surgery (cardiac pacemaker/defibrillator or other implanted devices).
* Inability or unwillingness to comply with long-term follow-up.
* History of intolerance to neural stimulation of any area of the body.
* Participation in another drug, device or biologics trial within the preceding 30 days.
* Conditions requiring repeated MRI scans.
* Conditions requiring diathermy.
* Conditions requiring anticoagulant medication.
* Terminal illness associated with expected survival of \<12 months.

Primary outcomes:
measure: Device Was Functioning
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected from 1 to 6 years.
measure: Mean Hamilton Depression Rating Scale (HDRS-17) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected for 1 to 2 years.
measure: Mean Hamilton Depression Rating Scale-21 (HDRS-21) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected for 1 to 2 years.
measure: Mean Hamilton Depression Rating Scale-24 (HDRS-24) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected for 1 to 2 years.
measure: Mean Hamilton Depression Rating Scale-28 (HDRS-28) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
measure: Mean Montgomery-Åsberg Depression Rating Scale (MADRS) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
measure: Mean Hamilton Anxiety Rating Scale Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
measure: Mean Young Mania Rating Scale (YMRS) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
measure: Mean Beck Depression Inventory-II (BDI-II) Score Over Time
timeFrame: Data was to be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
measure: Mean Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) Score Over Time
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or year 2 and 3 after implantation.
measure: Mean Global Assessment of Functioning (GAF) Score Over Time
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months); Data were collected at 1 year after impanation or 2 years after implantation.
measure: Number of Participants Reporting Suicidal Behavior or Actual Attempts Using the Columbia- Suicide Severity Rating Scale (C-SSRS) Over Time
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
measure: Number of Participants Reporting a Specific Value in the Severity of Illness Section of the Clinical Global Impressions (CGI) Assessment
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
measure: Number of Participants Reporting a Specific Value in the Global Improvement Section of the Clinical Global Impressions Assessment
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
measure: Number of Participants Providing a Specific Response Using the Patient Global Impressions (PGI) of Change Scale
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
measure: Number of Participants Providing a Specific Response Using the Patient Global Impressions (PGI) of Severity Scale
timeFrame: Data will be collected every year (approximately every 12 months) for up to 10 Years after the implantation of the device (approximately 120 months). Data were collected at 1 year after impanation or 2 years after implantation.
Secondary outcomes:
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
References: