Opioid-Related Disorders
Conditions
Keywords
Deep Brain Stimulation
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. This study will also provide critical information for planning subsequent clinical trials.
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.
Interventions
DEVICEDeep Brain Simulator
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.
Sponsors
National Institute on Drug Abuse (NIDA)
Medtronic
West Virginia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Study-Emergent Adverse Events | Enrollment - 52 weeks | Study participants will be closely monitored for adverse events following DBS surgery with regular check-ups by study personnel. |
| Change in Opioid Use | 12 weeks | Opioid use as measured by quantitative urine toxicology via high pressure liquid chromatography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Retention | 12 - 52 weeks | Participants' retention in traditional medication assisted treatment (MAT). |
| Mood, Craving and Executive Function | 12 and 24 weeks post surgery | Participants will complete standardized measures of mood, drug craving, and executive function at 12 weeks and 24 weeks post DBS titration. |
| Incidence of Serious Infectious Disease Complications | 12 - 52 weeks | Laboratory tests and evaluation to discern presentation of infectious disease. |
| Participant Survival | 12 -52 weeks | Incidence of drug overdose deaths among the participants. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frontal Lobe Metabolism | 3 weeks and 12 weeks post surgery | 18fluoro-Deoxy-Glucose (FDG) PET will be use to determine if there is an increase in frontal lobe metabolism following DBS |
| Changes in Dopamine | 3 weeks and 12 weeks post surgery | C11 Raclopride PET may be used to examine for changes in dopamine at 12 weeks post titration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OUD DBS 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.
Deep Brain Simulator: 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. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | OUD DBS |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
Change in Opioid Use
Opioid use as measured by quantitative urine toxicology via high pressure liquid chromatography.
Time frame: 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OUD DBS | Change in Opioid Use | Number of Participant's Opioid Negative through 12 Week Endpoint | 2 participants |
| OUD DBS | Change in Opioid Use | Number of Participant's Opioid Positive through 12 Week Endpoint | 2 participants |
Primary
Total Number of Study-Emergent Adverse Events
Study participants will be closely monitored for adverse events following DBS surgery with regular check-ups by study personnel.
Time frame: Enrollment - 52 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Unrelated | 20 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Severe AE - Unlikely Related | 2 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Total Mild AEs | 74 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Unexpected | 32 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE- Expected | 42 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Total Moderate AEs | 29 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Unexpected | 20 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Expected | 9 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Total Severe AEs | 5 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Severe AE - Unexpected | 4 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Severe AE - Expected | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Definitely Related (Surgical Procedure) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Definitely Related (Disorder) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Probably Related (Surgical Procedure/Stimulation) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Probably Related (Stimulation) | 2 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Probably Related (Disorder) | 30 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Possibly Related (Stimulation/Disorder) | 4 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Possibly Related (Stimulation) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Possibly Related (Disorder) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Unlikely Related | 6 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Mild AE - Unrelated | 27 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Probably Related (Surgical Procedure) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Probably Related (Stimulation/Disorder) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Probably Related (Disorder) | 5 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Possibly Related (Disorder) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Moderate AE - Unlikely Related | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Severe AE - Possibly Related (Surgical Procedure) | 1 Adverse Events |
| OUD DBS | Total Number of Study-Emergent Adverse Events | Severe AE - Possibly Related (Disorder) | 2 Adverse Events |
Secondary
Incidence of Serious Infectious Disease Complications
Laboratory tests and evaluation to discern presentation of infectious disease.
Time frame: 12 - 52 weeks
Secondary
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.
Time frame: 12 and 24 weeks post surgery
Secondary
Participant Survival
Incidence of drug overdose deaths among the participants.
Time frame: 12 -52 weeks
Secondary
Treatment Retention
Participants' retention in traditional medication assisted treatment (MAT).
Time frame: 12 - 52 weeks
Other Pre-specified
Changes in Dopamine
C11 Raclopride PET may be used to examine for changes in dopamine at 12 weeks post titration.
Time frame: 3 weeks and 12 weeks post surgery
Other Pre-specified
Frontal Lobe Metabolism
18fluoro-Deoxy-Glucose (FDG) PET will be use to determine if there is an increase in frontal lobe metabolism following DBS
Time frame: 3 weeks and 12 weeks post surgery