Efficacy and Safety of Dual-target Deep Brain Stimulation 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: NCT05884619
• Other study ID #: SR1182-AUD-I
• Status: Recruiting
• Phase: N/A
• Start date: August 14, 2023
• Est. completion date: December 30, 2024

Study information

• Verified date: September 2023
• Source: Second Xiangya Hospital of Central South University
• Contact: Wei Hao
• Phone: +8613907484086
• Email: weihao57[@]163.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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

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	Huashan Hospital	Shanghai	Shanghai
China	Shanghai 6th People's Hospital	Shanghai	Shanghai
China	Shanghai Mental Health Center	Shanghai	Shanghai

Sponsors (5)

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

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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.
Other	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
Primary	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
Primary	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
Primary	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	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
Secondary	Cumulated alcohol abstinent days	total value of 'Constant alcohol suspension' days	9-32 weeks of stimulation.
Secondary	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
Secondary	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
Secondary	Sleep status	Pittsburgh Sleep Quality Index score compared to baseline.	At 12, 20 and 32 weeks of stimulation
Secondary	affect status	Hamilton Anxiety Scale-17 and Hamilton Depression Scale score compared to baseline.	At 12, 20 and 32 weeks of stimulation
Secondary	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