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

Alcohol Use Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05786872
• Other study ID #: MZhao-012
• Status: Recruiting
• Phase: N/A
• Start date: July 5, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2023
• Source: Shanghai Mental Health Center
• Contact: Min Zhao
• Phone: 64387250
• Email: drminzhao[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Deep Brain Stimulation

Intervention

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.

Locations

Country	Name	City	State
China	Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (5)

Lead Sponsor	Collaborator
Shanghai Mental Health Center	Central South University, Huashan Hospital, SceneRay Corporation, Limited, Shanghai 6th People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Other	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)
Other	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.
Primary	Major alcohol use rate	Calculation formula: 'major alcohol use' times / 56 (total observation times) * 100%	24 weeks
Primary	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
Primary	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	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
Secondary	Cumulated alcohol suspension days	total value of 'Constant alcohol suspension' days after 9-32 weeks of stimulation.	24 weeks
Secondary	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
Secondary	Alcohol abstinence	Change in CIWA-Ar score compared to baseline.	At 12, 20 and 32 weeks of stimulation
Secondary	Sleep condition	Pittsburgh Sleep Quality Index score compared to baseline.	At 12, 20 and 32 weeks of stimulation
Secondary	Emotion condition	Hamilton Anxiety Scale-17 and Hamilton Depression Scale score compared to baseline.	At 12, 20 and 32 weeks of stimulation
Secondary	Social functions	SDSS score compared to baseline.	At 12, 20 and 32 weeks of stimulation