Efficacy and Safety of Dual-target Deep Brain Stimulation 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 meet inclusion and don't meet exclusion criteria are recruited to undergo neurosurgical implantation of dual-target DBS in bilateral nucleus accumbens (NAcc) and anterior limb of internal capsule (ALIC) on Day 0. The DBS system will be turned on for stimulation and parameter adjustment will be conducted on day 10-14 after implantation. The efficacy and safety evaluation will be conducted in 9-32 weeks after implantation. The indicators on efficacy are heaving drinking rate, uncontrolled alcohol consumption days, maximum consecutive alcohol abstinent days. The indicators for safety are 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, imaging 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: Wei Hao; Phone Number: +8613907484086; Email: weihao57@163.com

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Second Xiangya Hospital of Central South University
      • Contact: Wei Hao; Phone Number: +8613907484086; Email: weihao57@163.com
      • Principal Investigator: Wei Hao
      • Principal Investigator: Mengqiang Yu
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
      • Principal Investigator: Min Zhao
      • Contact: Min Zhao; Phone Number: +8618017311005; Email: drminzhao@gmail.com
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital
      • Principal Investigator: Liang Chen
      • Contact: Liang Chen; Phone Number: +8613661882460
    • Shanghai, Shanghai, China, 200233
      • Recruiting
      • Shanghai 6th People's Hospital
      • Contact: Wanhai Ding; Phone Number: +8618930170125
      • Principal Investigator: Wanhai Ding

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 to 65 years old, no limit on sex.
2. Meet The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for alcohol use diagnosis with more than 4 positive items.
3. Course of alcohol use disorder ≥ 3 years.
4. Had at least 3 failed quit drinking experiences (de-addiction treatment under medical conditions, quit drinking by oneself, quit drinking each time ≥ 1 week)
5. 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:

1. Patients with other serious mental disorders (e.g. schizophrenia spectrum, depression disorder, biphasic or related disorder, etc. )
2. Patients who have other substance (other than tobacco) use disorders.
3. During screening period, answered 'yes' on question 4 or 5 in suicide intention term from Columbia-Suicide Severity Rating Scale, or had significant suicidal ideations 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.
5. 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.
6. HIV positive patients.
7. Woman at pregnant or lactation period, or childbearing age woman test positive for human chorionic gonadotropin (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.
8. Patients who are participating other pharmaceutical or medical device clinical trials or have participated one in the past 3 months.
9. 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 and don't fit exclusion criteria, 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
Heavy drinking rate	Calculation formula: 'major alcohol use' times / 56 (total observation times) * 100%; 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.	9-32 weeks of stimulation
Cumulated uncontrolled alcohol use days	Total days of all uncontrolled alcohol use days throughout 24 weeks; 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	9-32 weeks of stimulation
Maximum consecutive alcohol abstinent days	Constant alcohol suspension standard: Blow test negative and no alcohol use reported over past 3 days. Marked as maximum days of 'Constant alcohol suspension'	9-32 weeks of stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol use volume	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.	9-32 weeks after stimulation
Cumulated alcohol abstinent days	total value of 'Constant alcohol suspension' days	9-32 weeks of stimulation.
Subjective alcohol craving	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
Sleep status	Pittsburgh Sleep Quality Index score compared to baseline.	At 12, 20 and 32 weeks of stimulation
affect status	Hamilton Anxiety Scale-17 and Hamilton Depression Scale score compared to baseline.	At 12, 20 and 32 weeks of stimulation
Alcohol withdrawal scores	change in Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) score compared to baseline. Minimum score is 0, maximum score is 67, higher the score, alcohol withdrawal is more severe (worse outcome).	At 12, 20 and 32 weeks of stimulation
Social functionings	Substance Dependence Severity Scale (SDSS) score compared to baseline. Minimum score is 0, maximum score is 20, higher the score, substance dependence is more severe (worse outcome).	At 12, 20 and 32 weeks of stimulation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrophysiology indicators	Before stimulation and parameter optimization period, DBS brain electrophysiology study will be conducted, such as electroencephalogram, target Local Field Potential; Observe instant effect to participants at stimulation onset (including instant desire change, emotional change, behavioral change of experimental psychological paradigm and change in brain electrophysiological indicators etc. ), thus to provide evidence for parameter adjustment for the study).	Before stimulation and parameter optimization period
Incidence of adverse events and related data	Adverse events (AE) and device-related adverse events.; Serious adverse events (SAE) and device-related serious adverse events.; Device deficiencies and device malfunctions.; Physical examination and vital signs.; Laboratory check: blood reverse transcription (RT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fbg, liver/kidney functions, liver ultrasonic and ECG.; Imaging examination: CT or MRI.; Early drop out ratio due to adverse events.	Collect security data throughout the research period, including AE, SAE, etc.
Positron Emission Topography imaging indicators	Before DBS implant, use Positron Emission Topography (PET) to study imaging of brain metabolism, receptor and structures. Metabolism features (DA, GABA, Glu) of brain areas including DLPFC, medial prefrontal prefrontal cortex, NAcc, dorsal striatum etc. will be the focus. Patients will be retested for PET after 6 months of implant.	Before stimulation and parameter optimization period

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University
• Collaborators: Huashan Hospital; Shanghai Mental Health Center; Shanghai 6th People's Hospital; SceneRay Corporation, Limited
• Investigators: Study Chair: Min Zhao, Shanghai Mental Health Center; Study Chair: Wei Hao, Second Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: May 23, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Alcohol Drinking; Alcoholism; Alcohol-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Substance-Related Disorders; Drinking Behavior
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism
• Other Study ID Numbers: SR1182-AUD-I

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