Deep Brain Stimulation Effects In Patients With Opioid Use Disorder

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

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Device: DBS of the NAc

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Donald Whiting, MD; Phone Number: 412-359-6200; Email: donald.whiting@ahn.org
• Study Contact Backup: Name: Nestor Tomycz, MD; Phone Number: 412-359-6200; Email: nestor.tomycz@ahn.org

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Recruiting
      • AHN Allegheny General Hospital
      • Sub-Investigator: Carol Schramke, PhD
      • Sub-Investigator: Amanda Webb, PA
      • Sub-Investigator: Stuart Fisk, CRNP
      • Contact: Clinical Trials Contact; Phone Number: 412-330-6151; Email: clinicaltrials@ahn.org
      • Principal Investigator: Nestor Tomycz, MD
      • Sub-Investigator: Donald Whiting, MD
      • Sub-Investigator: Heather Richards, MD
      • Sub-Investigator: Elizabeth Cuevas, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. OUD must be the primary disorder
3. 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.
4. 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
5. No active ilicit substance abuse as based on urine testing
6. Has completed a neuro-psychological evaluation to the satisfaction of a neuropsychologist
7. Has completed a psychiatric evaluation to the satisfaction of a psychiatrist
8. Has had a brain MRI performed and reviewed by neurosurgeon with no contraindication for DBS procedure identified
9. Platelet count > 125,000 per cubic mm and prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits
10. Negative blood cultures to rule out bacteremia

Exclusion Criteria:

1. Prior brain surgery
2. 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
3. History of suicide attempt in the past 5 years
4. History of uncontrolled or persistent seizures
5. Suspected dementia based on neuropsychological screening or Mini Mental State Exam (MMSE) Score < 25

6. Contraindications for MRI:

   1. Presence of implanted electrical stimulation device or other implanted metal devices (excluding dental braces).
   2. Claustrophobia
   3. Body weight exceeding limit of the machine (180 kg/400 lb)
7. 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.
8. Coagulopathy secondary to chronic need for anticoagulation medicine (e.g. warfarin) or anti-platelet medication (e.g. aspirin or clopidogrel)
9. Diagnosis of neurological disorders (e.g. multiple sclerosis, Parkinson's disease, and stroke)
10. Severe brain atrophy or presence of subdural hygromas or subdural hematomas on brain MRI
11. Any evidence of underlying endocarditis.
12. Primary language other than English
13. Have any other medical condition that, in the opinion of the Investigator, makes the subject unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NAc DBS; Subjects will receive bilateral DBS of the NAc

Device: DBS of the NAc; Deep Brain Stimulation of the Nucleus Accumbens; Other Names: Abbott Infinity DBS lead, model 6173ANS; Abbott Infinity DBS extension, model 6371ANS; Abbott Infinity DBS implantable pulse generator, model 6660ANS; Abbott Infinity DBS guardian burr hole cap, model 6010ANS; Abbott Infinity DBS patient controller, model 6883ANS; Abbott Infinity DBS clinician programmer, model 3872ANS

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Objective - Complication rates	Adverse events	12 months

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Collaborators: Abbott
• Investigators: Principal Investigator: Nestor Tomycz, MD, Allegheny Health Network

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Addiction; Nucleus Accumbens
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Opioid-Related Disorders
• Other Study ID Numbers: Addiction DBS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes