DBS of the Lateral Habenula in Treatment-Resistant Depression

NCT01798407 | Active Not Recruiting DMC FDA Device

• 5 other identifiers: H4030749593277909HSM#12-00467GCO 12-1815
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This research study will investigate the safety, tolerability, and benefit of bilateral deep brain stimulation (DBS) to the lateral habenula in subjects with treatment-resistant major depression (TRD) secondary to either nonpsychotic unipolar major depressive disorder (MDD), or bipolar disorder (BD) I. Six adult subjects with TRD will be treated in this single-site study at Baylor College of Medicine; subjects will be chronically symptomatic with significant functional disability, and will have demonstrated resistance to standard somatic and pharmacotherapeutic treatments. The primary outcome measure will be the change in the 17-item Hamilton Depression Rating Scale (HDRS\^17) six months after the commencement of stimulation.

Conditions

Treatment Resistant Major Depressive Disorder

Keywords

Deep Brain Stimulation; Major Depressive Disorder; Depression; Lateral Habenula; Intractable Depression; Treatment Resistant Depression (TRD)

Outcome Measures

Primary Outcomes (1)

• Change in HDRS^17 score from baseline to 6 months after the commencement of stimulation

  'Response' is categorically defined as a ≥ 50% reduction in the HDRS17 score relative to the baseline assessment. 'Remission' is defined as an absolute HDRS17 score \< 8. Study success criteria will be defined as ≥ 3 of the 6 patients meeting the individual subject success criteria of response or remission by HDRS17 score at the 6 month time point.

  baseline, Month 6, Month 12 and 18 months

Secondary Outcomes (10)

• MADRS (Montgomery and Asberg Depression Rating Scale)

  baseline, Month 6, Month 12 and 18 months

• Clinical Global Impression of Severity (CGI-S)

  baseline, Month 6, Month 12 and 18 months

• Clinical Global Impression of Improvement (CGI-I)

  baseline, Month 6, Month 12 and 18 months

• Young Mania Rating Scale (YMRS)

  baseline, Month 6, Month 12 and 18 months

• Columbia Suicide Severity Rating Scale (C-SSRS)

  baseline, Month 6, Month 12 and 18 months

Study Arms (2)

Activa Tremor Control Sys (DBS Implant)

EXPERIMENTAL

all subjects will receive bilateral surgical implantation of DBS system. Those who respond at 12 months will enter a randomized, staggered withdrawal phase.

Device: Activa Tremor Control Sys (DBS Implant)

Randomized, staggered withdrawal phase

EXPERIMENTAL

For responders only: double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen biweekly until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.

Other: Randomized, staggered withdrawal phase

Interventions

Activa Tremor Control Sys (DBS Implant) DEVICE

DBS system consists of the Activa RC 37612 System (Implantable Pulse Generator with Model 37085 Extensions (40 to 95cm), Activa Patient Programmer, and Medtronic Model 3389 DBS Lead). This system is commercially approved for the treatment of chronic, intractable Parkinson's Disease. It will be used with the Model SP-10344 Memory Mod Software which enables the physician to program the Implantable Pulse Generator to a higher frequency.

Also known as: Deep Brain Stimulation System, DBS, Activa RC System

Activa Tremor Control Sys (DBS Implant)

Randomized, staggered withdrawal phase OTHER

For responders only: double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen biweekly until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.

Randomized, staggered withdrawal phase

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women (non-pregnant) between ages 21 and 70;
• DSM-5 diagnosis (assessed by Structured Clinical Interview for DSM-5, SCID-5) of a current major depressive episode (MDE), recurrent or single episode with first episode before age 45, secondary to either nonpsychotic unipolar major depressive disorder (MDD)or bipolar disorder (BD) I;
• Chronic illness with current MDE ≥ 24 months duration and/or recurrent illness with at least a total of 4 lifetime episodes (including current episode ≥ 12 months);
• For subjects with a bipolar disorder: the last manic or hypomanic episode must have been ≥ 24 months before study enrollment and patients must be maintained on a mood stabilizer (e.g. lithium or another mood stabilizer approved for bipolar disorder).
• Treatment resistance (defined by criteria on the Antidepressant Treatment History Form): Failure (i.e. persistence of the major depressive episode) to respond to a minimum of three adequate depression treatments from at least two different treatment categories (e.g. SSRI's, TCA's, other antidepressants, lithium-addition, irreversible MAO-inhibitor, antidepressant augmentation with an atypical antipsychotic medication); also, if diagnosed as bipolar, failure to respond to (or inability to tolerate) a minimum of three treatments approved for bipolar disorder, including lithium and at least one medication FDA-approved for bipolar depression (e.g., olanzapine/fluoxetine combination, quetiapine, lurasidone).
• Previous trial of ECT (lifetime)
• Symptom Severity: HDRS17 ≥ 21; on two separate assessments (at initial screening and 1 week before surgery), over a 1-month period;
• Normal brain MRI within 3 months of surgery;
• Stable antidepressant medical regimen for the month preceding surgery
• Modified mini-mental state examination (MMSE) score ≥ 27;
• Normal thyroid stimulating hormone (TSH) level within 12 months of study entry;
• Other medical conditions must be stable for at least 1 year;
• Anticipates a stable psychotropic medication regimen in the next 24 months;
• Subject must be able to identify a family member, physician, or friend who will participate in the Treatment Contract;
• Able and willing to give informed consent.

You may not qualify if:

• Schizophrenia Spectrum or Other Psychotic Disorders (excluding Schizotypal (Personality) Disorder and Substance/Medication Induced Psychotic Disorder); presence of primary or serious (requiring additional treatment) disorders: comorbid obsessive compulsive disorder, post-traumatic stress disorder, panic disorder, bulimia or anorexia, in the last year;
• Cluster A or B personality disorder;
• Alcohol or substance abuse/dependence within 6 months, excluding nicotine and cannabis provided that participant either a) has a legal prescription or b) is a legal resident of a state where recreational cannabis use is legal;
• Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or had a serious suicide attempt within the last year;
• Neurological disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication (e.g., Parkinson's disease, MS, stroke);
• Any history of seizure disorder or hemorrhagic stroke;
• Any medical contraindication to surgery, including infection or coagulopathy;
• Participation in another drug, device, or biological trial within 30 days;
• Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators including spinal cord stimulators, and deep brain stimulators;
• Does not have adequate family/friend support as determined by psychological screening and/or interview;
• Abnormal brain MRI;
• Unable to maintain a stable psychotropic medication regimen in the next 24 months
• Pregnant or has plans to become pregnant in the next 24 months.

Sponsors & Collaborators

• Wayne Goodman MD: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (29)

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MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Depressive Disorder, Treatment-Resistant

Interventions

Deep Brain Stimulation; Random Allocation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Wayne K Goodman, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During staggered withdrawal phase, double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen every 2 weeks until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator; Chairman

Model Details: all subjects will receive bilateral surgical implantation of DBS system. Those who respond at 12 months will enter a randomized, staggered withdrawal phase. See masking description below.

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: February 25, 2013
• Study Start: February 1, 2013
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)