Deep Brain Stimulation of Nucleus Accumbens for Opioid Relapse Prevention

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

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.

Study Overview

• Status: Unknown
• Conditions: Addiction
• Intervention / Treatment: Device: Suzhou Sceneray® DBS System

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Recruiting
      • National Institute on Drug Dependence, Peking University
      • Contact: Lin Lu, M.D.; Phone Number: +86 13801027748; Email: linlu@bjmu.edu.cn
      • Contact: Jie Shi, M.D.; Phone Number: +86 13910710407
      • Principal Investigator: Lin Lu, M.D.
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital Southern Medical University
      • Contact: Kaijun Yang, M.D.; Phone Number: +86 13380082493
      • Sub-Investigator: Kaijun Yang, M.D.
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Recruiting
      • Department of Neurosurgery, Tangdu Hospital
      • Contact: Guodong Gao, M.D.; Phone Number: +86 29 84717556; Email: gguodong@fmmu.edu.cn
      • Contact: Xuelian Wang, M.D.; Phone Number: +86 29 84777284; Email: wxlian@fmmu.edu.cn
      • Principal Investigator: Guodong Gao, M.D.
      • Sub-Investigator: Xuelian Wang, M.D.
  • Shanghai
    • Shanghai, Shanghai, China, 200020
      • Recruiting
      • Ruijin Hospital
      • Contact: Bomin Sun, M.D.; Phone Number: +86 13817777401; Email: bominsun@sh163a.sta.net.cn
      • Principal Investigator: Bomin Sun, M.D.
  • Si Chuan
    • Chengdu, Si Chuan, China, 610041
      • Recruiting
      • West China Hospital
      • Contact: Wei Wang, M.D.; Phone Number: +86 13808170699

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years old < Age < 50 years old

• Moderate to severe opiates abuse disorders (fulfilled diagnostic-criteria according to DSM-5)

  1. History of opiates abuse no less than 3 years
  2. Failure of at least three addiction treatments ( in hospital or compulsive rehabilitation）, among which failure of methadone maintenance treatment must be met
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Postoperative immediate Deep brain stimulation; 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; 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.
Sham Comparator: Postoperative delayed Deep brain stimulation; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Collaborators: Peking University First Hospital; West China Hospital; Nanfang Hospital of Southern Medical University; Ruijin Hospital; National Institute on Drug Dependence, Peking University
• Investigators: Principal Investigator: Guodong Gao, M.D., Department of Neurosurgery, Tangdu Hospital; Principal Investigator: Lin Lu, M.D., National Institute on Drug Dependence, Peking University

Publications and helpful links

General Publications

• Qu L, Ge S, Li N, Wang W, Yang K, Wu P, Wang X, Shi J. Clinical evaluation of deep brain stimulation of nucleus accumbens/anterior limb of internal capsule for opioid relapse prevention: protocol of a multicentre, prospective and double-blinded study. BMJ Open. 2019 Feb 13;9(2):e023516. doi: 10.1136/bmjopen-2018-023516.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 6, 2018
• Primary Completion (Anticipated): January 30, 2020
• Study Completion (Anticipated): January 30, 2020

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 7, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: January 31, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Deep brain stimulation; Opiate dependence; Nucleus accumbens
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Compulsive Behavior; Impulsive Behavior; Recurrence; Behavior, Addictive
• Other Study ID Numbers: NAcDBSORP

Drug and device information, study documents

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