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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder; Deep Brain Stimulation
• Intervention / Treatment: Device: dual-target deep brain stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Min Zhao; Phone Number: 64387250; Email: drminzhao@gmail.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Second Xiangya Hospital of Central South University
      • Contact: Wei Hao, doctor; Phone Number: 13661882460
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai Mental Health Center
      • Contact: Min Zhao, doctor; Phone Number: 18017311005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: dual-target deep brain stimulation; 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; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain electrophysiology study（electroencephalogram）	Electroencephalographic rhythms (theta and beta) were recorded. And theta/beta ratio was compared to before stimulation	Before stimulation and parameter optimization period(1-8 weeks after stimulation)
Brain electrophysiology study（Local Field Potentials）	Electrical signal strength was compared to before stimulation	Before stimulation and parameter optimization period(1-8 weeks after stimulation)
PET-CT	Before DBS implant, use Positron Emission Topography (PET) technology to study imaging of brain metabolism. Metabolism features include the amount of dopamine, gamma-aminobutyric acid, glutamate. Patients will be retested for PET after 6 months of implant.	Before DBS implant, after 6 months of implant.

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Huashan Hospital; Central South University; Shanghai 6th People's Hospital; SceneRay Corporation, Limited
• Investigators: Study Chair: MIn Zhao, Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 26, 2023
• First Submitted That Met QC Criteria: March 26, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: MZhao-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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