Efficacy and Safety of Nerve Growth Factor or Edaravone on Alcohol-induced Brain Injury

Study Overview
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Brief Summary
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Alcohol is one of most common harmful substance, and alcohol intake brings great burden on health worldwide. Excess alcohol intake may lead to alcohol-related brain injuries and cognitive impairment. Although both nerve growth factor and antioxidative treatment were effective to relieve alcohol-related injuries in central nervous system in the preclinical studies, there is no relevant clinical trial about their efficacy and safety on patients. Since nerve growth factor and one of the antioxidative medication, edaravone, have been used in some neural diseases in clinical trials, we tend to evaluate the efficacy and safety of nerve growth factor, or edaravone on alcohol-induced brain injuries. The study is a randomized-controlled study and the patients will be assigned into one of the following three groups randomly: (1) regular treatment (combination of vitamin B1, B6, C, E and mecobalamine) with nerve growth factor for 2 weeks and subsequently regular treatment for 6 months; (2) regular treatment (RT) with edaravone for 2 weeks and subsequently RT for 6 months; (3) RT alone for 6 months. The patients will be followed up for 6 months. Cognitive functions, recurrence of alcohol dependence, duration of abstention, alcohol intake, craving for alcohol and other psychological assessments will be recorded and compared among the 3 treatment groups and the efficacy of nerve growth factor or edaravone will be evaluated in our study.

Official Title
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Efficacy and Safety of Nerve Growth Factor or Edaravone on Alcohol-induced Brain Injury

Conditions
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Alcohol-induced Brain Injury

Intervention / Treatment
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* Drug: Nerve Growth Factor
* Drug: Edaravone
* Drug: Combination of vitamin B1, B6, C, E and mecobalamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis as alcohol dependence according to DSM-IV criteria MRI-proved demyelinating lesions or atrophy in the brain of the patient No definite history of neurological diseases and psychological problems Volunteer to participate the study, cooperate to be followed up Exclusion Criteria: Acute withdrawal state and CIWA score > 9 With other neurological diseases and psychological problems With ever brain trauma and damage With other psychological medications or other substance dependence

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Regular treatment (RT)<br>Combination of vitamin B1, B6, C, E and mecobalamine | Drug: Combination of vitamin B1, B6, C, E and mecobalamine<br>* Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months<br>|
| Experimental: RT with NGF<br>Nerve growth factor adding to regular treatment | Drug: Nerve Growth Factor<br>* Intramuscular injection for 2 weeks<br>Drug: Combination of vitamin B1, B6, C, E and mecobalamine<br>* Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months<br>|
| Experimental: RT with EDV<br>Edaravone adding to regular treatment | Drug: Edaravone<br>* Intravenous injection for 2 weeks<br>Drug: Combination of vitamin B1, B6, C, E and mecobalamine<br>* Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive improvement | Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function. | 2 weeks | 
| Cognitive improvement | Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function. | 2 months | 
| Cognitive improvement | Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function. | 3 months | 
| Cognitive improvement | Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function. | 6 months | 
| Cognitive assessment | Cognitive assessment by Montreal Cognitive Assessment (MoCA) ranging from 0 to 30. Lower score indicates worse cognitive function. | 3 months | 
| Cognitive assessment | Cognitive assessment by Montreal Cognitive Assessment (MoCA) ranging from 0 to 30. Lower score indicates worse cognitive function. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of relapse of alcohol dependence after discharge from hospital | Recurrence of alcohol dependence | 2 months | 
| Duration of abstinence | The total time or period without any intake of alcohol during follow ups | 6 months | 
| Alcohol intake | Diaries of alcohol intake in different time of the follow ups | 2 weeks, 2 months, 3 months, 6 months | 
| Craving for alcohol | Craving assessment for alcohol by Obsessive Compulsive Drinking Scale (OCDS) ranging from 0 to 40. Higher score of OCDS indicates more desire for alcohol. | 2 weeks, 2 months, 3 months, 6 months | 
| Psychological assessment - Anxiety | Psychological assessment by Generalized Anxiety Disorder-7 (GAD-7) ranging from 0 to 21. Higher score indicates more severer anxiety. | 2 weeks, 2 months, 3 months, 6 months | 
| Psychological assessment - Depression | Psychological assessment by Patient Health Questionnaire-9 (PHQ-9) ranging from 0 to 27. Higher score indicates more severer depression. | 2 weeks, 2 months, 3 months, 6 months | 
| Psychological assessment - Sleep | Psychological assessment by Pittsburgh Sleep Quality Index (PSQI) ranging from 0 to 21. Higher score indicates worse sleep. | 2 weeks, 2 months, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol-induced brain injury, atrophy, demyelination