A Clinical Pilot Study Examining Bilateral Inhibition of the Lateral Habenula as a Target for Deep Brain Stimulation in Intractable Depression
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 6
- Locations
- 2
- Primary Endpoint
- Change in HDRS^17 score from baseline to 6 months after the commencement of stimulation
Study Overview
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.
Detailed Description
This research study includes the following parts: 1. medical, psychiatric, and cognitive evaluations 2. implantation of the brain stimulation system, and 3. follow up including programming and psychiatric testing after the implantation
- Medical, psychiatric, and cognitive evaluations:
For those subjects that are found to be eligible and agree to participate in the study, they will be asked more detailed questions about their symptoms, mood, and thinking on another visit before receiving the implantation. The investigator will ask detailed questions about the subject's psychiatric and medical history, and will ask for a list of medications along with response to previous treatments. The subject will also be asked to fill out several questionnaires.
Subjects will be asked to give a sample of both blood and urine for standard lab evaluations. All subjects will be tested for the presence of drugs of abuse in their urine. All women of child bearing potential will also be tested for pregnancy. If any of the test results are positive, the subject cannot continue to be part of this study, but can receive other standard clinical care by a treating psychiatrist.
As part of the pre-operative clinical evaluation, all subjects will be evaluated by a neurosurgeon, and, potentially, a medical specialist for surgical optimization, as well as an anesthesiologist for an intra-operative risk assessment. Prior to surgery, an independent evaluator who is not affiliated with the research study will confirm the diagnosis of MDD and assess the subject's understanding of the risks of the surgery and follow-up care.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
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.
Eligibility Criteria
- Ages
- 21 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Change in HDRS^17 score from baseline to 6 months after the commencement of stimulation
Time Frame: baseline, Month 6, Month 12 and 18 months
'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.
Secondary Outcomes
- MADRS (Montgomery and Asberg Depression Rating Scale)(baseline, Month 6, Month 12 and 18 months)
- Clinical Global Impression of Improvement (CGI-I)(baseline, Month 6, Month 12 and 18 months)
- QIDS-SR (Quick Inventory of Depressive Symptomatology)(baseline, Month 6, Month 12 and 18 months)
- Generalized Anxiety Disorder 7-item Scale (GAD-7)(baseline, Month 6, Month 12 and 18 months)
- Sheehan Disability Scale(baseline, Month 6, Month 12 and 18 months)
- Clinical Global Impression of Severity (CGI-S)(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)
- Neuropsychological Battery(baseline, Month 6, Month 12 and 18 months)
- PRISE (The Patient Rated Inventory of Side Effects)(baseline, Month 6, Month 12 and 18 months)
Investigators
Wayne Goodman MD
Principal Investigator; Chairman
Baylor College of Medicine