Deep Brain Stimulation of Nucleus Accumbens for Opioid Relapse Prevention

Study Overview
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Brief Summary
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Nucleus accumbens plays important roles in the process of opiate addiction and initial of relapse after detoxification.According to the single-centered preliminary open-labeled prospective trial results, the investigators hypothesize that bilateral stimulation of the NAc will effectively reduce the relapse of the opiate dependence.

Official Title
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Deep Brain Stimulation of Nucleus Accumbens for Opioid Relapse Prevention:A Multicenter Randomized Double-Blind Sham-stimulation Controlled Clinical Trial

Conditions
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Addiction

Intervention / Treatment
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* Device: Suzhou Sceneray® DBS System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old < Age < 50 years old Moderate to severe opiates abuse disorders (fulfilled diagnostic-criteria according to DSM-5) History of opiates abuse no less than 3 years Failure of at least three addiction treatments ( in hospital or compulsive rehabilitation）, among which failure of methadone maintenance treatment must be met completion of detoxification ( Negative urine test for morphine, methamphetamine, ketamine and buprenorphine) Free patient's decision/informed Consent (existing comprehensive ability in meaning, methodology and execution of the study and ability of acceptance, known the benefit and risk of the treatment) Exclusion Criteria: Clinical relevant psychiatric comorbidity (schizophrenic psychoses, bipolar affective diseases, severe personality disorder) Contraindications of a MRI-examination, e.g. implanted cardiac pacemaker/heart defibrillator Abuse of other type of drugs severe cognitive impairments Enrollment in other clinical trials Stereotactic respectively neurosurgical intervention in the past Contraindications of a stereotactic operation, e.g. increased bleeding-disposition, cerebrovascular diseases (e.g. arteriovenous malfunction, aneurysms, systemic vascular diseases) Serious and instable organic diseases (e.g. instable coronal heart disease) tested positively for HIV pregnancy and/or lactation Severe disorders for coagulation and liver function Epilepsy or other severe brain trauma or neurological impairments

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Stagger-on design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Postoperative immediate Deep brain stimulation<br>The addicts undergone the deep brain stimulation while the stimulation (Suzhou Sceneray® DBS System) was turned on 1-2 weeks postoperatively. | Device: Suzhou Sceneray® DBS System<br>* We plan to use the SceneRay 1242 (SceneRay, SuZhou, China) electrode with a diameter of 1.27 mm and 4 contacts. The SceneRay 1242 electrode combined with the SceneRay 1181 implantable pulse generator has the advantage of adaptive coverage area for the Ventral Capsule/Ventral Striatum, enabling simultaneous implantation in the nucleus accumbens (NAc; 2 ventral contacts) and the anterior limb of the internal capsule (ALIC; 2 dorsal contacts) with independently programmed parameters such as frequency, amplitude, and voltage; and remote and wireless programing, which allows for convenient and prompt adjustments in emergency situations.<br>|
| Sham Comparator: Postoperative delayed Deep brain stimulation<br>The addicts undergone the deep brain stimulation while the stimulation (Suzhou Sceneray® DBS System) was off until 25 months postoperatively, during which the following up was kept, then the the stimulation was turned on 25 months postoperatively. | Device: Suzhou Sceneray® DBS System<br>* We plan to use the SceneRay 1242 (SceneRay, SuZhou, China) electrode with a diameter of 1.27 mm and 4 contacts. The SceneRay 1242 electrode combined with the SceneRay 1181 implantable pulse generator has the advantage of adaptive coverage area for the Ventral Capsule/Ventral Striatum, enabling simultaneous implantation in the nucleus accumbens (NAc; 2 ventral contacts) and the anterior limb of the internal capsule (ALIC; 2 dorsal contacts) with independently programmed parameters such as frequency, amplitude, and voltage; and remote and wireless programing, which allows for convenient and prompt adjustments in emergency situations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The abstinent rate at 25 weeks after DBS stimulation on （Urine Tests） | If the participants or their families report no less than 2 times of the drug use in each of two consecutive weeks, or the consecutive 2 times of urine tests showed positive, or lost of follow-up, the case was defined as relapse | At 25 weeks after DBS stimulation on | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The total days of abstinence for participants | The total days of abstinence for participants | Baseline (preoperative), 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| The longest duration for sustained abstinence for participants | The longest duration for sustained abstinence for participants | Baseline (preoperative), 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Visual analog scale (VAS) craving score for opioid drugs | Ranging from 0-10,with 0 indicates no craving while 10 indicates extreme craving | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Body weight for participants | Body weight for participants | Baseline (preoperative), 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Hamilton Depression Scale（HAMD-17) | 17 items,Total scores<7: normal;7<Total scores<17:possible depression;17<Total scores<24:definite depression;Total score>24: severe depression | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Scaling for Opiate withdrawal symptoms | There were 19 items for rating 19 withdrawl symptoms, with 0 indicating none and 4 indicating most severe, the total scores are obtained by summary for scores of each items, ranging from 0-76, the higher the total scores indicating the worsen opiate withdrawl symptoms. | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| The evaluation on MATRICS-test | Software system constructed by MATRICS company, which was used for evaluate the cognitive function of the participants | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| The rate of positive urine test results | times of positive urine test/ total times of urine test | Baseline (preoperative), 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Hamilton Anxiety Scale (HAMA) | 14 items, Total scores<6: normal;7<Total scores<14:possible anxiety;14<Total scores<21:definite anxiety;Total score>21: severe anxiety | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Pittsburgh sleep quality index(PSQI) | Scaling for evaluating the sleep quality, the higher total scores indicating the more difficulties on sleep, thus the higher total scores indicating the worsen sleep quality | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Fagerstrom Test Nicotine Dependence assessment (FTND) | Scaling for Nicotine Dependence: The higher of scores indicating higher lever of Nicotine Dependence | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Social Disability Screening Schedule (SDSS) | Scaling for Social Disability with 10 items, the higher total scores indicating the much severe social disability | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| Activity of Daily Living Scale (ADL) | Consists of Physical Self-maintenance Scale and Instrumental Activities of Daily Living Scale, ranging from 0-56, total scores <14, normal; total score >14, ADL dysfunction | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 
| 36-Item Short Form Health Survey (SF-36) | Scaling for Quality of life with 8 subscales, the higher total scores indicating the better quality of life. | Baseline (preoperative), 1week, 4 weeks, 12 weeks, 25 week after DBS stimulation on | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opiate dependence, Deep brain stimulation, Nucleus accumbens