Deep Brain Stimulation for Major Depressive Disorder

Abbott Medical Devices125 enrolled

Overview

This study is designed as a prospective, multi-centered, double-blind, randomized, controlled 12-month pivotal study to evaluate the safety and efficacy of the ANS Libra® Deep Brain Stimulation System for patients with major depressive disorder who have failed at least 4 treatments in the current episode. The primary outcome assessment will occur at 6 months: however, all patients will be followed for 1 year. A total of 201 patients will be randomized from up to 20 sites. Each potential patient will be pre-screened according to the inclusion/exclusion criteria. A narrative of what study participation entails, will be used to educate potential participants on study requirements. Prior to on-site baseline evaluations, the patient will sign the informed consent. Patients will then undergo 3 baseline evaluations, with each of these evaluations to occur no less than 2 weeks apart from each other. The first 2 baseline visit evaluations will be performed by separate psychiatrists in order to confirm the patient's diagnosis. All patients will be scheduled for surgery, to occur no less than two weeks and no more than 1 month after final baseline evaluation, to implant the ANS Libra® Deep Brain Stimulation system. After device implantation, patients will be randomly assigned to 1 of 2 groups in a 2:1 ratio (Active Treatment Group \& Control Group). After system implant (Week 0), the patient will return to clinic approximately 2 weeks after surgery for evaluation and treatment randomization into either Group 1 or Group 2 (Group 1 = Active Treatment Group; Group 2 = Control Group). Patient will then return to clinic for subsequent evaluations at 2 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, and 1 year post system implantation.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

125

Eligibility

Sex: ALLMin age: 21 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Men and women (non-pregnant) age is 21-70 years; 2. Diagnosed with non-psychotic major depressive disorder, single or recurrent episode by DSM-IV-TR criteria derived from the MINI; 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's, SNRI's, TCA'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. 15. During last 6 months in the current episode documented treatment under the care of a licensed psychiatrist/psychologist. Exclusion Criteria: 1. A diagnosis of a bipolar I or bipolar II disorder by DSM-IV-TR criteria, derived from the MINI; 2. Meets criteria for borderline or antisocial personality disorder in the last 12 months by DSM-IV-TR criteria, derived from the Cluster B Personality Disorders Sections 301.7 - 301.83, and screened via SCID-II at Baseline visit; 3. In the current depressive episode, has been diagnosed with General Anxiety Disorder (GAD) - as defined by the DSM-IV-TR, and GAD is the primary diagnosis; 4. Has an intracranial Central Nervous System (CNS) disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication (e.g., Parkinson's Disease, chronic migraine, stroke, Huntington's, head trauma, etc.) with exception to non-migraine headaches; 5. Has been diagnosed with fibromyalgia or has a current condition which requires chronic pain narcotic usage (e.g. morphine, methadone); 6. Has been currently diagnosed with chronic fatigue syndrome; 7. Substantial suicidal risk as defined by (1) MADRS item 10 score of 5 or 6, (2) a current plan and intent,(3) clinician judgment that there is a clear immediate intent for self-harm, (4) more than 3 suicide attempts within the last 12 months; 8. Co-morbid obsessive compulsive disorder, posttraumatic stress disorder, panic disorder, bulimia or anorexia nervosa if previously present, must be in remission for 6 months as defined by DSM-IV-TR criteria, derived from the MINI; 9. Alcohol, medication, or illegal substance dependence or abuse within last 12 months derived from the MINI; 10. Diagnosis of sleep apnea confirmed by a sleep test that is not adequately treated; 11. Advanced cardiovascular disease which renders anesthesia and surgery as unsafe as determined by neurosurgeon; 12. Clinically relevant abnormality (e.g. tumor or growth) on study MRI; 13. Has cardiac pacemaker/defibrillator or other implanted active stimulator; 14. Has a medical condition requiring a repetitive MRI body scan; 15. Requires chemotherapy for the treatment of malignancy or requiring chronic oral or intravenous (immunosuppressive or) steroid therapy; 16. Is unable to comply with study visit schedule and timeline; 17. Past ablative or relevant intracranial surgery; 18. A female lactating or of child bearing potential, with a positive pregnancy test or not using adequate contraception; 19. Lifetime psychotic disorders, schizophrenia, or schizoaffective disorder defined by DSM-IV-TR; 20. Psychotic features in current depressive episode as diagnosed by DSM-IV-TR criteria; 21. Other medical conditions likely to require hospitalization within the next year; 22. Received ECT within 3 months prior to enrollment, or requires ECT for the duration of the study; 23. Has a history of epilepsy or history of status epilepticus; 24. Plans to use diathermy; 25. Has any metallic implants such as aneurysm clips or cochlear implants; 26. Currently participating in another investigational device, drug or surgical trial

Locations (13)

Stanford University School of Medicine

Stanford, California, United States

Alexian Brothers Behavioral Health Hospital

Chicago, Illinois, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

University of Minnesota Medical School

Minneapolis, Minnesota, United States

The Zucker Hillside Hospital

Glen Oaks, New York, United States

Columbia University Medical Center

New York, New York, United States

Medical Univeristy of South Carolina (MUSC)

Charleston, South Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

...and 3 more locations

Outcomes

Primary Outcomes

Montgomery and Asberg Depression Rating Scale (MADRS) Score at Baseline and the Average of Months 4, 5, and 6

The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen.

Time frame: Baseline to 6 months

Secondary Outcomes

Baseline MADRS to MADRS at 1 Year

Time frame: Baseline to 1 year

Number of Participants With Adverse Events (i.e., Hospitalization Due to Worsening Depression, Suicidal Ideation or Behavior, Medical Treatment, and Device Related Events) That Occur Over Study Duration

Time frame: 6 months-1 year

Global Assessment Scale (GAF) Score at Baseline and 1 Year

The Global Assessment Scale (GAF) is a hypothetical continuum of mental health illness that looks at psychological, social, and occupational functioning. It measures how much a person's symptoms affect their day to-day life on a scale of 0 to 100. A score of 100-91 indicates no symptoms, 90-81 indicates absent minimal symptoms, 80-71 indicates symptoms that are transient and reactions expectable to psychosocial stressors, 70-61 indicates mild symptoms, 60-51 indicates moderate symptoms, 50-41 indicates serious symptoms, 40-31 indicates some impairment in reality testing or communication OR major impairment in several areas, 30-21 indicates delusions or hallucinations, 20-11 indicates danger of hurting self or others OR occasionally fails to maintain personal hygiene, 10-1 indicates persistent danger of severely hurting self or others OR persistent inability to maintain minimal personal hygiene OR serious suicidal act with clear expectation of death and 0 indicates inadequate data.

Time frame: 1 year

Hamilton Rating Scale for Depression - 17 Item (HRSD-17) Score at Baseline and 6 Months

The Hamilton Rating Scale for Depression - 17 item (HDRS-17) ranging from 0-52 used to assess potential changes in the severity of depressive symptoms (Hamilton 1960; Hamilton 1967). It is used to evaluate depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. Scoring is based on the 17-itemscale and scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52 on the17-point scale.

Time frame: 6 months

Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Score From Baseline to 1 Year

The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a self-report instrument designed to measure the degree of enjoyment and satisfaction experienced by subjects in various areas of daily functioning. There are 16 areas of functioning, each scored from 1 (very poor) to 5 (very good). The range of scores is 16-80, with lower scores representing lower functioning and satisfaction.

Time frame: 1 year

Inventory of Depressive Symptomology (IDS-C30) Score From Baseline to 1 Year

The construction of the Inventory of Depressive Symptomology (IDS-C30) was intended to remedy deficits in the Hamilton Scale for Depression (HRSD-17) and Montgomery and Asberg (MADRS) depression rating scales by, among others, including all nine symptom domains needed to diagnose a DSM-IV major depressive episode in order to assess symptom remission, improve ability to detect milder levels of symptoms than the HRSD-17, and provide unconfined and more equivalent weighting among items. There are two versions of the IDS with identical items: a clinician rating (IDS-C30) and a self-report (IDS-SR30). Each of the 30 items is rated from 0 to 3, with increasing severity represented by a higher rating. (Rush et al. 1996). When complete, the IDS-C30 and IDS-SR30 are scored by summing responses to 28 of the 30 items to obtain a total score ranging from 0 to 84. Either appetite increase or decrease, but not both, are used to calculate the total score.

Time frame: 1 year

Quick Inventory of Depressive Symptomatology (QIDS-SR) Scores From Baseline to 1 Year

The Quick Inventory of Depressive Symptomatology Self Report (QIDS- SR) is a 16-question shortened self-test, derived from the 30-item IDS. Questions in the QIDS - SR-116 correlate with the nine DSM-IV symptom criterion domains, including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). The severity of depression can be judged based on the total score ranging from 1-27. A score of 1-5 indicates No depression, 6-10 indicates Mild depression,11-15 indicates Moderate depression, 16-20 indicates Severe depression and 21-27 indicates Very severe depression.

Time frame: 1 year

Work and Social Adjustment Scale (WSAS) Score From Baseline to 1 Year

The WSAS is a modification of a scale introduced by Hafner and Marks (1976), consisting of 0-8 point ratings of the extent to which symptoms interfere with five areas of daily functioning: work, home management, private leisure, social leisure, and family relationships. It is a well-validated, widely used self-report measure. Additional time points include weeks 4, 8, 12, 16, and 40. A total score calculated as a sum of all items (possible range 0-40) was used in the analyses with higher scores indicating more impairment.

Time frame: 1 year

Deep Brain Stimulation for Major Depressive Disorder

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes