Deep Brain Stimulation (DBS) Therapy for Treatment Resistant Depression
We propose a clinical study of medial forebrain bundle DBS as a treatment in 10 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Activa® systems manufactured by Medtronic Neurological will be used in this study. Study subjects will be between the ages of 22 and 65 years of age and suffer from TRD, have failed multiple treatment regimens, including ECT, and remain symptomatic. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
Major Depressive Disorder
Treatment Resistant Depression
Device: Deep Brain Stimulation Model 3387 Model 3389
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
|Official Title:||Deep Brain Stimulation (DBS) Therapy for Treatment Resistant|
- Changes in patients MADRS scores [ Time Frame: weekly (24 Months) ] [ Designated as safety issue: Yes ]We will assess individual patient response, measured by standardized patient and clinician ratings of depression severity, under blinded conditions. Prospective ratings using validated and reliable measures of symptoms, quality of life and safety will be employed. We will assess safety for all subjects by monitoring any adverse events.
- Accuracy of Electrode placement [ Time Frame: Post-operation (weekly for 24 months) ] [ Designated as safety issue: No ]We will implant the Model 3387/Model 3389 lead at this target location, with the exact choice of lead to be determined during surgery.
- Frequency and Charge of Stimulation [ Time Frame: Weekly (24 months total) ] [ Designated as safety issue: No ]The optimal stimulation parameters for reducing depressive symptoms acutely and chronically are unknown. Preliminary data suggest that psychiatric patients who have responded to DBS have responded at high frequencies and amplitudes that presumably induce a depolarization block or "neuronal jamming," and thus mimic a lesion. We intend to explore the effects of a wide range of frequencies and amplitudes during the acute testing phase and to utilize high frequency continuous stimulation at the lowest amplitude that results in a definitive effect in the chronic phase of the study.
- Determine Feasibility of a Double Blind Study [ Time Frame: 24 months ] [ Designated as safety issue: No ]We hypothesize that it will be possible to develop a suitable double-blind procedure by which neither patients nor physicians will know whether DBS is on or off at any given moment.
- Decrease in Neurocognitive scores on CSTC [ Time Frame: pre-operative, 12 month and 24 months post-operation ] [ Designated as safety issue: No ]In this study, neuropsychological tests believed sensitive to changes in Concept Shifting Test-Combined (CSTC) function, and particularly orbitofrontal function, will be obtained with the stimulator on and off, if possible, under blinded conditions. In a separate study, positron emission tomography (PET) perfusion imaging and neuropsychological tests will be obtained to determine how corticobasal brain function changes after acute and chronic DBS.
- Assess maintenance of treatment response (or remission) associated with chronic DBS: [ Time Frame: 6, 12, and 24 months ] [ Designated as safety issue: No ]Maintaining Treatment Response
- Number of Adverse Events [ Time Frame: 24 months (reported weekly) ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Experimental: Deep Brain Stimulation
Device implantation (Deep Brain Stimulation Model 3387 Model 3389)
Device: Deep Brain Stimulation Model 3387 Model 3389
Implantation of all devices will be performed at a single session. Lead implantation will take place under local anesthesia, with implanted pulse generator (IPG) implantation under general anesthesia. The stereotaxic frame will be fitted on the day of surgery, following standard stereotactic surgical procedure. The leads will be inserted so that the stimulation sites span superolateral median forebrain bundle.
Other Name: Medtronic Neuromodulation
Study Design: Subjects will be ten patients with MDD identified via the Structured Clinical Interview for DSM-IV, manifesting a current major depressive episode of disabling severity, refractory to prolonged treatment trials with conventional medication, electro-convulsive therapy (ECT) and psychotherapy. A marked impact of depression on their health and functional status will be evidenced by major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior). They will be recruited from individuals currently seen at our facility or referred by psychiatrists in the community. Patients will be initially screened by a comprehensive review of their psychiatric history, obtained by interview of the patient, family and treating psychiatrist and/or psychologist, as well as by obtaining and reviewing all available records of previous psychiatric treatment. The available generally-accepted alternative treatments for depression are pharmacologic therapy, psychotherapy, and ECT. Failed trials of multiple proven pharmacologic treatments, an adequate course of psychotherapy, and an adequate course of bilateral ECT (or inability to tolerate an adequate ECT trial) are inclusion criteria for all candidates who are considered for this study. However, as alternatives to participation in this study, candidates may undertake additional trials of potentially beneficial novel combinations of medication and psychotherapy, or they may undertake trials of novel interventions lacking definitive evidence of efficacy in severe depression (e.g., light therapy, herbal therapy, transcranial magnetic stimulation, vagal nerve stimulation). The protocol was designed to include four phases. All patients will enter these phases in the same sequence. The experimental design is illustrated in the timeline in Figure 1. Surgical implantation will be followed by: 1) Baseline Phase (a 1 month period with no stimulation); 2) Variable Staggered Phase (blinded stimulation onset starting from 1 month to 3 months post implant, with optimal parameter determination during this time ; 3) Initial Chronic Phase (blinded bilateral stimulation, lasting at least three months) (see below); 4) Continuation Phase (unblinded active bilateral or unilateral stimulation to maximize clinical response) Protocol overview and design: We propose a clinical study of medial forebrain bundle DBS as a treatment in 10 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Activa® systems manufactured by Medtronic Neurological will be used in this study. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02046330
|Contact: Jair C Soares, MD, PhDfirstname.lastname@example.org|
|Contact: Danielle E Spiker, BAemail@example.com|
|United States, Texas|
|UT Center of Excellence on Mood Disorders||Recruiting|
|Houston, Texas, United States, 77054|
|Contact: Jair C Soares, MD 713-486-2627 firstname.lastname@example.org|
|Contact: Giovana Zunta-Soares, MD 713-486-2629 email@example.com|
|Principal Investigator: Jair C Soares, MD|
|Principal Investigator:||Jair C Soares, MD, PhD||The University of Texas Health Science Center, Houston|