Efficacy and Safety of Dual-target DBS for Treatment-resistant Alcohol Use Disorder

Study Overview
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Brief Summary
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This is a multi-center, single arm, prospective, open-label, extendable study for the efficacy and safety of dual-target deep brain stimulation for treatment-resistant alcohol use disorder.

Detailed Description
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Total of 12 subjects from two centers ( Shanghai Mental Health Center and The Second Xiangya Hospital of Central South University ) who fit inclusion and exclusion criteria are recruited to undergo neurosurgical implantation of dual-target Deep Brain Stimulation (DBS) in bilateral nucleus accumbens (NAcc) and anterior limb of internal capsule (ALIC) on a certain date, the DBS system will be turned on for stimulation and parameters adjusted 10-14 days after implantation, treatment purposes are evaluated after DBS system has been turned on for 9-32 weeks. Primary efficacy is evaluated by major alcohol consumption rate, uncontrolled alcohol consumption days, maximum consecutive alcohol suspension days. Safety is evaluated by adverse events (AE) and device related AE, serious adverse events (SAE) and device related SAE, device deficiencies (DD) and device malfunction, physical examination and vital signs, laboratory examination, ECG, imageological examination, scale evaluation and early drop out ratio due to AE.

Official Title
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Efficacy and Safety of Dual-target Deep Brain Stimulation for Treatment-resistant Alcohol Use Disorder: a Multi-center, Single Arm, Prospective, Open-label, Extendable Study

Conditions
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Deep Brain Stimulation, Alcohol Use Disorder

Intervention / Treatment
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* Device: dual-target deep brain stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 65 years old, no limit on sex. Qualifies DSM-5 definition of alcohol use diagnosis, at least more than 4 terms. Course of alcohol use disorder ≥ 3 years. Tried to quit drinking (de-addiction treatment under medical conditions, quit drinking by oneself, quit drinking each time ≥ 1 week) but failed ≥ 3 times. Patient and relatives agree to accept systemic treatment of this study and sign Informed Consent Form after study purpose, content, expected treatment and risk etc. are fully explained and understood. Exclusion Criteria: Patients who qualify DSM-5 serious mental disorder diagnosis standard (e.g. Schizophrenia spectrum, depression disorder, biphasic or related disorder, etc. ) Patients who have other substance (tobacco excluded) abuse. During screening period, answered 'yes' on question 4 or 5 in suicide intention term from Columbia-Suicide Severity Rating Scale, or had significant suicide intentions in the past 3 months, or patients who are considered by researchers to have suicide or violence risks. 4. Patients who have serious or unstable cardiovascular, respiratory, liver, kidney, hematological, endocrine, nervous system or other systemic diseases. Patients who have implanted cochlear, pacemaker, cardiac defibrillator, single-sided or double-sided products of the same category, or the investigator evaluates patients have done surgeries within 6 months that can affect this study. HIV positive patients. Woman at pregnant or lactation period, or childbearing age woman test positive for HCG/urine pregnancy check; or patients who can't take effective contraception measures during trial; or patients who plan to be/make pregnant 3 months after the trial starts. Patients who are participating other pharmaceutical or medical device clinical trials or have participated one in the past 3 months. Patients who are considered unsuitable by investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dual-target deep brain stimulation<br>This is a single arm, prospective, open label clinical study, participants who fit inclusion/exclusion standards, completed physical anti-addiction treatments and surgical implantation standard will start DBS system stimulation and adjust parameters after 10-14 days of implantation. Then after stimulation for 9-32 weeks, they will be evaluated for treatment efficacies. This study is extendable, with agreements from participants, long term efficacy and safety follow-up study will be performed after 32 weeks ± 7 days of following, once every 2-3 months. | Device: dual-target deep brain stimulation<br>* DBS electrodes will be implanted into the ALIC and the NAcc, electric stimulation of those areas are used to treat alcohol use disorder and to evaluate the efficacy and safety of DBS system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major alcohol use rate | Calculation formula: 'major alcohol use' times / 56 (total observation times) * 100% | 24 weeks | 
| Cumulated uncontrolled alcohol use days | Definition: more than 3 times consecutive alcohol use (random draw) ≥ 5 standard cups One time uncontrolled alcohol use days: e.g. 3 times consecutive follow-up results ≥ 5 standard cups, fourth time < 5 standard cups, then uncontrolled alcohol use days is 3 * 3 = 9 days Cumulated uncontrolled alcohol use days: Total days of all uncontrolled alcohol use days throughout 24 weeks | 24 weeks | 
| Maximum consecutive alcohol suspension days | a) Marked as maximum days of 'Constant alcohol suspension' b) Note: i. Major alcohol use standard: Blow test positive and reported ≥ 5 standard cups daily over the past 3 days. 1 standard cup = 10g of pure alcohol. ii. Minor alcohol use standard: No matter blow test is positive or not, alcohol use is reported over past 3 days but less than 5 standard cups. iii. Constant alcohol suspension standard: Blow test negative and no alcohol use reported over past 3 days. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol use volume | 9-32 weeks after stimulation, change in monthly average alcohol use volume compared to baseline. (Record in every follow-up according to participants. Record alcohol type, amount and experience when drinking throughout 9-32 weeks after stimulation. Increased value implies worse result and reduce of alcohol use volume indicates improvement. | 24 weeks | 
| Cumulated alcohol suspension days | total value of 'Constant alcohol suspension' days after 9-32 weeks of stimulation. | 24 weeks | 
| Subjective alcohol urge | Change in alcohol urge Visual Analogue Score compared to baseline. ( 0 is no urge, 10 is extreme urge) | At 12, 20 and 32 weeks of stimulation | 
| Alcohol abstinence | Change in CIWA-Ar score compared to baseline. | At 12, 20 and 32 weeks of stimulation | 
| Sleep condition | Pittsburgh Sleep Quality Index score compared to baseline. | At 12, 20 and 32 weeks of stimulation | 
| Emotion condition | Hamilton Anxiety Scale-17 and Hamilton Depression Scale score compared to baseline. | At 12, 20 and 32 weeks of stimulation | 
| Social functions | SDSS score compared to baseline. | At 12, 20 and 32 weeks of stimulation |