Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder

Study Overview
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Brief Summary
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The purpose of this clinical study is to investigate the safety, tolerability, and feasibility of Deep Brain Stimulation (DBS) of the nucleus accumbens (NAc) and ventral internal capsule (VC) for participants with treatment refractory opioid use disorder (OUD) who have cognitive, behavioral, and functional disability. This study will also provide critical information for planning subsequent clinical trials.

Detailed Description
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The overarching goal of this study is to evaluate the safety, tolerability, feasibility and impact on outcomes of NAc/VC DBS for treatment refractory OUD. In treatment refractory OUD, innovative approaches and more invasive interventions including DBS are warranted to improve outcomes.

Official Title
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Feasibility of Deep Brain Stimulation as a Novel Treatment for Refractory

Conditions
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Opioid-Related Disorders

Intervention / Treatment
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* Device: Deep Brain Simulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfills current DSM-5 (American Psychiatric Association Diagnostic and statistical manual of mental disorders, 5th ed, 2013) diagnostic criteria for OUD (severe) and at least a 5-year history. Participants may have comorbid SUD diagnoses at mild, moderate or severe levels, however OUD must be the primary disorder for which the individual is seeking treatment and the other use disorders must occur in the context of relapse Failed at least two levels of treatment (outpatient/Comprehensive Opioid Addiction Treatment (COAT), intensive outpatient/intensive COAT, residential, inpatient, Adult Intensive Outpatient Program (AIOP), Dual Diagnosis Unit (DDU), which included buprenorphine/naloxone. At least two overdose survivals or one overdose survival and one life-threatening infectious disease complication with relapse after treatment (e.g., endocarditis with valve repair/replacement) within the past 1 year. Family/Social Support/Involvement (as assessed via the Multidimensional Scale of Perceived Social Support). Is able to provide informed consent. Exclusion Criteria: Medical problems requiring intensive medical or diagnostic management. Diagnosis of acute myocardial infarction or cardiac arrest within the previous 6 months. History of a neurosurgical ablation procedure. Any medical contraindications to undergoing DBS surgery. History of hemorrhagic stroke. Life expectancy of <3 years Past or present diagnosis of schizophrenia, psychotic disorder, bipolar disorder, or untreated depression other than one determined to be substance induced (assessed via SCID-5). Any treated depression has to have been in remission for one year. Baseline assessment on the Hamilton Depression Rating Scale (HAMD) of greater than 17 or increased risk of suicide based upon any positive response on the Columbia Suicide Severity Scale. Cluster A or B Personality Disorders. Diagnosis of dementia. History of neurological disorder. History of previous neurosurgery (brain) or head trauma. History of suicide attempt. Parental history of completed suicide. Abnormal coagulation lab studies or uncontrolled hypertension. Implanted neurostimulators. Any current CNS infection or infection with the Human Immunodeficiency Virus (HIV). Unable to undergo MR-imaging. Documentation of MRI abnormality indicative of a neurological condition. Substance abuse treatment mandated by court of law. Pregnant or planning to become pregnant. Conditions requiring diathermy. Anticoagulant treatment. Primary language other than English. Any evidence of systemic infection.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, safety, tolerability, and feasibility study for participants who have treatment refractory OUD that are eligible to have deep brain stimulation (DBS) targeting the NAc/VC.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OUD DBS<br>This is a single arm study. Participants will be followed in an inpatient service for two weeks to gather baseline data followed by DBS placement and up to 6 weeks inpatient for clinical stabilization and DBS titration. All participants will then be followed twice a week for 12 weeks in the outpatient setting and then once a week for a total of 52 weeks post-titration. | Device: Deep Brain Simulator<br>* This is an open-label, safety, tolerability, and feasibility study for participants who have treatment refractory OUD that are eligible to have DBS targeting the NAc/VC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Study-Emergent Adverse Events | Study participants will be closely monitored for adverse events following DBS surgery with regular check-ups by study personnel. | 24 - 52 weeks | 
| Change in Opioid Use | Opioid use as measured by quantitative urine toxicology via high pressure liquid chromatography. | 24 - 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Survival | Incidence of drug overdose deaths among the participants. | 12 -52 weeks | 
| Treatment Retention | Participants' retention in traditional medication assisted treatment (MAT). | 12 - 52 weeks | 
| Incidence of Serious Infectious Disease Complications | Laboratory tests and evaluation to discern presentation of infectious disease. | 12 - 52 weeks | 
| Mood, Craving and Executive Function | Participants will complete standardized measures of mood, drug craving, and executive function at 12 weeks and 24 weeks post DBS titration. | 12 and 24 weeks post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Brain Stimulation