Deep Brain Stimulation Effects In Patients With Opioid Use Disorder

Study Overview
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Brief Summary
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This is a pilot study to evaluate the safety and efficacy of deep brain stimulation (DBS) of the nucleus accumbens (NAc) as adjunctive treatment for treatment-refractory opioid use disorder. This study will include 3 individuals with opioid use disorder and relapsing opioid use despite active participation in a drug addiction treatment program.

Detailed Description
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Three (N = 3) subjects with treatment refractory opioid use disorder will receive bilateral DBS implants in the NAc using the Abbott Medical Infinity DBS system. The primary outcome of this study is to demonstrate the safety of bilateral NAc DBS in patients with treatment-refractory opioid use disorder. Secondary outcomes include time to relapse, remission of opioid use, and change in opioid craving scores. Other secondary outcomes will include the following: Hamilton Depression Scale (HDS), neurophysiological tests, body weight and biochemical markers of health and nutrition. If effective, DBS may reduce opioid use and opioid relapse in people with opioid use disorder who may continue to display relapse despite ongoing multidisciplinary standard of care. DBS brain electrode implantation and implantation of the IPGs and extension wires will be done in the operating room and will require the subject to be admitted post-operatively for an overnight stay. Two weeks after the DBS operation, subjects will undergo systematic testing each of the quadripolar contacts and formal programming. Subsequent parameter settings will be changed at routine outpatient visits based on clinical effects. Standard of care can consist of methadone or buprenorphine maintenance treatment provided by an addiction specialist.

Official Title
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Pilot Study to Evaluate Deep Brain Stimulation (DBS) of the Nucleus Accumbens (NAc) for Patients With Treatment-refractory Opioid Use Disorder

Conditions
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Opioid-use Disorder

Intervention / Treatment
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* Device: DBS of the NAc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and females age ≥ 22 years with diagnosis of opioid use disorder (OUD) based on Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) with at least a 5-year history OUD must be the primary disorder Failed at least two levels of treatment (Comprehensive Opioid Addiction Treatment (COAT), intensive outpatient COAT, residential, inpatient, alternative to intensive outpatient program, Drug Dependence Unit, which included buprenorphine/naloxone or buprenorphine monotherapy. Has exhibited more than 2 episodes of opioid use relapse in prior 12 months despite ongoing participation in MAT program, including either methadone or buprenorphine or suboxone No active ilicit substance abuse as based on urine testing Has completed a neuro-psychological evaluation to the satisfaction of a neuropsychologist Has completed a psychiatric evaluation to the satisfaction of a psychiatrist Has had a brain MRI performed and reviewed by neurosurgeon with no contraindication for DBS procedure identified Platelet count > 125,000 per cubic mm and prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits Negative blood cultures to rule out bacteremia Exclusion Criteria: Prior brain surgery 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 History of suicide attempt in the past 5 years History of uncontrolled or persistent seizures Suspected dementia based on neuropsychological screening or Mini Mental State Exam (MMSE) Score < 25 Contraindications for MRI: Presence of implanted electrical stimulation device or other implanted metal devices (excluding dental braces). Claustrophobia Body weight exceeding limit of the machine (180 kg/400 lb) Females who are pregnant or nursing. Female subjects of child-bearing potential must have a negative pregnancy test during the pre-op phase and must agree to utilize adequate birth control throughout the trial and for at least 30 days following trial completion. Coagulopathy secondary to chronic need for anticoagulation medicine (e.g. warfarin) or anti-platelet medication (e.g. aspirin or clopidogrel) Diagnosis of neurological disorders (e.g. multiple sclerosis, Parkinson's disease, and stroke) Severe brain atrophy or presence of subdural hygromas or subdural hematomas on brain MRI Any evidence of underlying endocarditis. Primary language other than English Have any other medical condition that, in the opinion of the Investigator, makes the subject unsuitable for enrollment.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAc DBS<br>Subjects will receive bilateral DBS of the NAc | Device: DBS of the NAc<br>* Deep Brain Stimulation of the Nucleus Accumbens<br>* Other names: Abbott Infinity DBS clinician programmer, model 3872ANS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid use/abstinence | Percentage of subjects achieving opioid abstinence | 6 months | 
| Opioid use/abstinence | Percentage of subjects achieving opioid abstinence | 1 year post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in biochemical markers of health | Biochemical battery of tests. Blood draw for plasma CBC, lytes, BUN, creatinine, Glutamate dehydrogenase (GLDH), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), erythrocyte mean corpuscular volume (MCV), carbohydrate-deficient transferrin (CDT) | Baseline, 6, 12 and 24 months | 
| Changes in biochemical markers of nutrition | Biochemical battery of tests. Blood draw for plasma, pre-albumin, folate, B12, calcium, magnesium, iron | Baseline, 6, 12 and 24 months | 
| Depression score | Hamilton Depression Scale: There are 17 items by which an assessor will select one cue which best characterizes the patient (0-4). All items are added up for a total score, where lower numbers are indicative of a normal score and higher numbers are indicative of worse depression. | Baseline, 3, 6, 9, 12 and 24 months post-surgery | 
| Quality of life measure | Flanagan QOL scale: Subjects will assign a rank score to 16 items. Rankings go from 7 to 1, where 7 is a better outcome and 1 is the worst outcome. The scale is as follows: 7=Delighted, 6=Pleased, 5=Mostly Satisfied, 4=Mixed, 3=Mostly Dissatisfied, 2=Unhappy, 1=Terrible. All rankings are totaled for a final score. | Baseline, 3, 6, 9, 12 and 24 months post-surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Brain Stimulation, Addiction, Nucleus Accumbens