Alcohol Use Disorder, Deep Brain Stimulation
Conditions
Keywords
Alcoholism, Alcohol Drinking, Drinking Behavior, Alcohol-Related Disorders, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorders
Brief 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.
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.
Interventions
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.
Sponsors
Shanghai Mental Health Center
Huashan Hospital
Shanghai 6th People's Hospital
SceneRay Corporation, Limited
Second Xiangya Hospital of Central South University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulated uncontrolled alcohol use days | 9-32 weeks of stimulation | Total days of all uncontrolled alcohol use days throughout 24 weeks 1. Definition: more than 3 times consecutive alcohol use (random draw) ≥ 5 standard cups 2. 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 3. Cumulated uncontrolled alcohol use days: Total days of all uncontrolled alcohol use days throughout 24 weeks |
| Maximum consecutive alcohol abstinent days | 9-32 weeks of stimulation | Constant alcohol suspension standard: Blow test negative and no alcohol use reported over past 3 days. Marked as maximum days of 'Constant alcohol suspension' |
| Heavy drinking rate | 9-32 weeks of stimulation | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective alcohol craving | At 12, 20 and 32 weeks of stimulation | change in alcohol urge Visual Analogue Score compared to baseline. ( 0 is no urge, 10 is extreme urge) |
| Sleep status | At 12, 20 and 32 weeks of stimulation | Pittsburgh Sleep Quality Index score compared to baseline. |
| affect status | At 12, 20 and 32 weeks of stimulation | Hamilton Anxiety Scale-17 and Hamilton Depression Scale score compared to baseline. |
| Social functionings | At 12, 20 and 32 weeks of stimulation | 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). |
| Alcohol withdrawal scores | At 12, 20 and 32 weeks of stimulation | 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). |
| 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. |
| Cumulated alcohol abstinent days | 9-32 weeks of stimulation. | total value of 'Constant alcohol suspension' days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Electrophysiology indicators | Before stimulation and parameter optimization period | 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). |
| Positron Emission Topography imaging indicators | Before stimulation and parameter optimization period | 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. |
| Incidence of adverse events and related data | Collect security data throughout the research period, including AE, SAE, etc. | 1. Adverse events (AE) and device-related adverse events. 2. Serious adverse events (SAE) and device-related serious adverse events. 3. Device deficiencies and device malfunctions. 4. Physical examination and vital signs. 5. 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. 6. Imaging examination: CT or MRI. 7. Early drop out ratio due to adverse events. |
Countries
China
Contacts
Primary ContactWei Hao
Outcome results
None listed