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.

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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A Randomized, Sham-Controlled Trial Investigating Deep Brain Stimulation as a Novel Treatment for Refractory Opioid Use Disorder

Conditions
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Opioid-Related Disorders

Intervention / Treatment
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* Device: Deep Brain Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 22-50 years at time of enrollment. Fulfills current DSM-5 diagnostic criteria for severe OUD with at least a 5-year history. Participants may have comorbid SUD diagnoses at a mild, moderate or severe level, 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. At least one lifetime overdose survival. Demonstrated greater than five years of refractory symptoms of OUD. Exclusion Criteria: Diagnosis of acute myocardial infarction or cardiac arrest 1 within the previous 6 months. Past or present diagnosis of schizophrenia, psychotic disorder, bipolar disorder, or untreated depression other than one determined to be substance induced. Unable to undergo MR-imaging

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 50 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBS-ON<br>Titration will be based on stimulation parameters used in previous studies examining the role of DBS of the NAc in the treatment o OCD and depression as well as the parameters utilized in the initial pilot study conducted by the team. | Device: Deep Brain Stimulation<br>* randomized, sham-controlled, partial crossover study investigating DBS, targeting the nucleus accumbens (NAc) and ventral internal capsule (VC), for participants with severe, treatment refractory OUD.<br>|
| Sham Comparator: DBS-OFF<br>For participants randomized to the DBS-OFF condition, titration sessions will be conducted identically to the DBS-ON arm, the only difference is that no stimulation is delivered and therefore, no actual adjustments made | Device: Deep Brain Stimulation<br>* randomized, sham-controlled, partial crossover study investigating DBS, targeting the nucleus accumbens (NAc) and ventral internal capsule (VC), for participants with severe, treatment refractory OUD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as measured by all adverse events related to DBS | Incidence of Study-Emergent Adverse Events. The safety/tolerability primary endpoint will be assessed comparing Grade 3 and 4 adverse events between the Active (DBS-ON) and Sham (DBS-OFF) arms throughout Phase IV (Outpatient Week 12). We will also categorize adverse events by organ system and assess relatedness to any aspect of this proof-of-concept study. Statistical tests will be performed at the request of the Data and Safety Monitoring Board (DSMB). | Outpatient Week 12 | 
| Opioid use assessed via quantitative urine toxicology | Opioid use will be evaluated through the use of quantitative urine toxicology using gas chromatography/mass spectrometry. For each subject, quantitative urine toxicology will be collected at baseline (during screening) and during Outpatient Follow-Up Week 4, 8, and 12. The primary outcome comparison between the active and sham arms will be the percentage of participants with undetectable opioid metabolites (assessed via quantitative urine toxicology) throughout the primary Outpatient Week 12 endpoint. | Outpatient Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Brain Reward Circuitry (FDG PET) | Changes in the reward circuitry via evaluating prefrontal cortex glucose metabolism (FDG PET) | Change from Baseline versus Outpatient Week 12 | 
| Changes in the Brain Reward Circuitry (Fallypride PET) | Changes in the reward circuitry via evaluating dopamine in the basal ganglia and NAc (18F-fallypride PET). | Change from Baseline versus Outpatient Week 12 | 
| Changes in Non-Cue Induced Substance Craving (Visual Analog Scale) | Substance craving without cues: Substance craving will be assessed using a visual analog scale (VAS) where participants are asked to rate their craving. Participants will be asked How much do you crave [insert substance name] right now?. Scale: 0 to 10 where 0 = no craving and 10 = maximum craving | Change from Baseline versus Outpatient Week 12 | 
| Changes in Cue-Induced Substance Craving (Visual Analog Scale) | Substance craving with cues (via a cue reactivity task): A set of substance-related stimuli (e.g., photos, computer images) will be presented to the participant. Prior to and immediately after viewing the cues, participants will complete computer-based assessment VAS designed to assess craving. Participants will be asked How much do you crave [insert substance name] right now?. Scale: 0 to 10 where 0 = no craving and 10 = maximum craving | Change from Baseline versus Outpatient Week 12 | 
| Changes in Mood and Emotional Functioning (Comprehensive Psychopathological Rating Scale) | Mood and emotional functioning (depression and anxiety) assessed via the Comprehensive Psychopathological Rating Scale (CPRS) Scale: 0 - 108 where 0 = no distress and 108 = severe distress | Change from Baseline versus Outpatient Week 12 | 
| Changes in Cognitive Functioning (NIH Toolbox Cognition Battery) | Cognitive Functioning assessed via NIH Toolbox Cognition Battery (NIHTB) | Change from Baseline versus Outpatient Week 12 | 
| Changes in Cognitive Functioning (Standard Neuropsychological Battery) | Cognitive Functioning assessed via the standard neuropsychological battery (e.g., WAIS-IV) | Change from Baseline versus Outpatient Week 12 | 
| Changes in Cognitive Functioning (Executive Functioning: Flanker, N-Back, Psychomotor Vigilance, Delayed Discounting) | Cognitive Functioning assessed via the experimental measures of executive functioning (e.g., Flanker, N-Back, Psychomotor Vigilance, Delayed Discounting). | Change from Baseline versus Outpatient Week 12 | 

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