A Clinical Evaluation for the Management of Patients with Major Depressive Disorder, Single or Recurrent Episode, with Deep Brain Stimulation - BROADEN

Summary

Study Summary: This study is designed as a prospective, multi-centered, double-blind, randomized, and controlled study to evaluate the safety and efficacy of the ANS Libra(TM) Deep Brain Stimulation System for patients with major depressive disorder whose depression has failed to respond to at least 4 antidepressant treatments in the current episode. The project consists of two parts and one substudy: Part I is the DBS Treatment (Surgical) Part and the length of participation for each patient will be approximately 13-14 months, which includes 4 weeks of screening, time to surgery (to occur no less than two weeks and no more than 1 month after final baseline evaluation) and 12 months of post surgery visits. The area of the brain to be stimulated is Brodmann Area 25 because it has been shown to be involved in both acute sadness and antidepressant treatment effects.

The primary outcome assessment will occur at 6 months from implant: however, all patients will be followed for 1 year.A total of 201 patients will be randomized from up to 20 sites. It is expected that twenty subjects will be screened locally to implant ten eligible patients. Patients will be randomized into one of two groups. Two-thirds of the patients will have stimulation activated (stimulation turned on) 2 weeks post-surgery. The other 1/3 will have their stimulation activated at 6 months.
An important issue that will be discussed with each patient will be the study requirement that they turn their psychiatric care over to a study investigator for the 12 month study period. The purpose of this is to ensure that, if possible, their current antidepressant medications be maintained at the same doses. This should allow any effect of the DBS to be more apparent.
The primary effectivness variable is change from baseline (mean of baselines 1,2, and 3) to the mean of months 4,5, and 6 in the MADRS. The primary endpoint is a clinical response defined as 40% or greater reduction from baseline in the MARDS plus no worsening in Global Assessment of Functioning.
Part II is the Long Term Follow-up study. Eligible participants will be enrolled in 4 year extension to evaluate safety and efficacy of the ANS Libra Deep Brain Stimulation System for patients with major depressive disorder.
Substudy is a Health Economic Evaluation to estimate incremental economic impact of DBS treatment for chronic or recurrent MDD versus incremental differences in effectiveness. This is for those participants enrolled in the DBS treatment study or those who will be enrolled in the future who have private or publicly funded insurance.

Participant Eligibility

Criteria for Inclusion of Subjects:
1) Men and women (non-pregnant) ages 21-70 years;
2) Diagnosed with non-psychotic major depressive disorder, single or recurrent episode by DSM-IV-TR criteria
3) First episode onset before age 45;
4) Current episode > 12 months duration;
5) In the current episode: Documented resistance (i.e. persistence of the major depressive episode) to a minimum of 4 adequate depression treatments from at least 3 different treatment categories (e.g. SSRI[Single Quote]s, SNRI[Single Quote]s, TCA[Single Quote]s, MAO-inhibitors, Mirtazipine, Nefazodone, Trazodone, Bupropion, lithium augmentation, thyroid augmentation, ECT); Adequacy of treatments as defined by a score of at least 3 according to the amended Antidepressant Treatment History Form (ATHF) criteria;
6) In Lifetime: Received a course of psychotherapy for depression;
7) Montgomery Asberg Depression Rating Scale (MADRS) of > 22 at 3 separate baseline visits, rated by 2 separate psychiatrists, Baseline 2 and Baseline 3 MADRS scores cannot be separated by > 6 weeks and cannot improve >= 20%;
8) Global Assessment of Function, score <50;
9) Modified mini-mental state examination (MMSE) score >24;
10)No change in current antidepressant medication regimen or medication free >4 weeks prior to study entry (with exception to sleep, cholesterol, blood pressure, sexual dysfunction, non-migraine headache medication, or medication for other medical reasons not related to depression, in which changes to dose or type will be allowed during course of study);
11) Able to give informed consent in accordance with institutional policies;
12) Able to comply with all testing and follow-up requirements as defined by the study protocol;
13) Must be determined medically stable by surgeon, to undergo deep brain stimulation surgical procedure.
14) Must have platelet count, PT and PTT within normal limits of the laboratory and/or determined to be not clinically significant prior to surgery as determined by the neurosurgeon.
15) Patients must currently be receiving care from a psychiatrist
Study Part II
1. Subjects who sign consent form for follow-up study
2. Subjects who completed the 12 month post surgery period of the part I of the study
3. Subjects who underwent the surgery implant but withdrew from the study before completing the surgery
4.Subjects who experience an increase in their depression symptoms reflected by a 25% increase in their MADRS score from baseline or subjects who become suicidal and could not be managed within the study protocol.

Substudy
Criteria for Inclusion of Subjects:
1.Subjects who have been or will be enrolled in the DBS treatment study (Study I) in the future, and who have private or publicly funded health insurance
2.Subjects who sign consent form and authorize release of their medical payment records for their health care service during the 12 months prior to entering the BROADEN study and for 12 month study period and the 48 months thereafter.