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

Sponsor

West Virginia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05903495

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Opioid-Related Disorders	Device: Deep Brain Stimulation	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

After completion of surgery, participants will be randomly assigned to one of two groups: Group A or Group B. Group A (DBS-ON) will have their stimulator turned on after recovering from surgery. Group B (DBS-OFF) will receive sham stimulation, meaning the stimulator will remain off until Study Week 12 of the outpatient phase, at which time the stimulator will be turned on and left on for the remainder of the study. Group A will continue to receive stimulation and not have the stimulator turned off. participant and assessor will not know which group are assigned to until Study Week 12.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DBS-ON 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 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.
Sham Comparator: DBS-OFF 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 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.

Arm

Intervention/Treatment

Experimental: DBS-ON

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

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.

Sham Comparator: DBS-OFF

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

Outcome Measures

Primary Outcome Measures

Safety and tolerability as measured by all adverse events related to DBS [Outpatient Week 12]
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).
Opioid use assessed via quantitative urine toxicology [Outpatient Week 12]
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.

Secondary Outcome Measures

Changes in the Brain Reward Circuitry (FDG PET) [Change from Baseline versus Outpatient Week 12]
Changes in the reward circuitry via evaluating prefrontal cortex glucose metabolism (FDG PET)
Changes in the Brain Reward Circuitry (Fallypride PET) [Change from Baseline versus Outpatient Week 12]
Changes in the reward circuitry via evaluating dopamine in the basal ganglia and NAc (18F-fallypride PET).
Changes in Non-Cue Induced Substance Craving (Visual Analog Scale) [Change from Baseline versus Outpatient Week 12]
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
Changes in Cue-Induced Substance Craving (Visual Analog Scale) [Change from Baseline versus Outpatient Week 12]
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
Changes in Mood and Emotional Functioning (Comprehensive Psychopathological Rating Scale) [Change from Baseline versus Outpatient Week 12]
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
Changes in Cognitive Functioning (NIH Toolbox Cognition Battery) [Change from Baseline versus Outpatient Week 12]
Cognitive Functioning assessed via NIH Toolbox Cognition Battery (NIHTB)
Changes in Cognitive Functioning (Standard Neuropsychological Battery) [Change from Baseline versus Outpatient Week 12]
Cognitive Functioning assessed via the standard neuropsychological battery (e.g., WAIS-IV)
Changes in Cognitive Functioning (Executive Functioning: Flanker, N-Back, Psychomotor Vigilance, Delayed Discounting) [Change from Baseline versus Outpatient Week 12]
Cognitive Functioning assessed via the experimental measures of executive functioning (e.g., Flanker, N-Back, Psychomotor Vigilance, Delayed Discounting).

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	West Virginia University Rockefeller Neuroscience Institute	Morgantown	West Virginia	United States	26505

Sponsors and Collaborators

West Virginia University
National Institute on Drug Abuse (NIDA)

Investigators

Study Director: James Mahoney, PhD, WVU Rockefeller Neuroscience Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

West Virginia University

ClinicalTrials.gov Identifier:

NCT05903495

Other Study ID Numbers:

2301715195

First Posted:

Jun 15, 2023

Last Update Posted:

Jun 15, 2023

Last Verified:

Jun 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Keywords provided by West Virginia University

Deep Brain Stimulation

Additional relevant MeSH terms:

Opioid-Related Disorders

Study Results

No Results Posted as of Jun 15, 2023