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

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.

Study Overview

• Status: Unknown
• Conditions: Alcohol-induced Brain Injury
• Intervention / Treatment: Drug: Combination of vitamin B1, B6, C, E and mecobalamine; Drug: Nerve Growth Factor; Drug: Edaravone

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Peng, MD, PhD; Phone Number: +86-13380051581; Email: pengy2@mail.sysu.edu.cn
• Study Contact Backup: Name: Hongxuan Wang, MD, PhD; Phone Number: +86-13824498978; Email: wanghx8@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Regular treatment (RT); Combination of vitamin B1, B6, C, E and mecobalamine	Drug: Combination of vitamin B1, B6, C, E and mecobalamine; Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months
EXPERIMENTAL: RT with NGF; Nerve growth factor adding to regular treatment	Drug: Combination of vitamin B1, B6, C, E and mecobalamine; Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months; Drug: Nerve Growth Factor; Intramuscular injection for 2 weeks
EXPERIMENTAL: RT with EDV; Edaravone adding to regular treatment	Drug: Combination of vitamin B1, B6, C, E and mecobalamine; Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months; Drug: Edaravone; Intravenous injection for 2 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Publications and helpful links

General Publications

• McArthur JC, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, Marra C, Rubin M, Cohen BA, Tucker T, Navia BA, Schifitto G, Katzenstein D, Rask C, Zaborski L, Smith ME, Shriver S, Millar L, Clifford DB, Karalnik IJ. A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. AIDS Clinical Trials Group Team 291. Neurology. 2000 Mar 14;54(5):1080-8. doi: 10.1212/wnl.54.5.1080. Erratum In: Neurology 2000 Jul 13;55(1):162.
• Sun YY, Li Y, Wali B, Li Y, Lee J, Heinmiller A, Abe K, Stein DG, Mao H, Sayeed I, Kuan CY. Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection. Stroke. 2015 Jul;46(7):1947-55. doi: 10.1161/STROKEAHA.115.009162. Epub 2015 Jun 9.
• Kaste M, Murayama S, Ford GA, Dippel DW, Walters MR, Tatlisumak T; MCI-186 study group. Safety, tolerability and pharmacokinetics of MCI-186 in patients with acute ischemic stroke: new formulation and dosing regimen. Cerebrovasc Dis. 2013;36(3):196-204. doi: 10.1159/000353680. Epub 2013 Oct 12. Erratum In: Cerebrovasc Dis. 2013;36(5-6):461.
• Munakata A, Ohkuma H, Nakano T, Shimamura N, Asano K, Naraoka M. Effect of a free radical scavenger, edaravone, in the treatment of patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2009 Mar;64(3):423-8; discussion 428-9. doi: 10.1227/01.NEU.0000338067.83059.EB.
• Writing Group; Edaravone (MCI-186) ALS 19 Study Group. Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017 Jul;16(7):505-512. doi: 10.1016/S1474-4422(17)30115-1. Epub 2017 May 15.
• Apfel SC, Kessler JA, Adornato BT, Litchy WJ, Sanders C, Rask CA. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. NGF Study Group. Neurology. 1998 Sep;51(3):695-702. doi: 10.1212/wnl.51.3.695.
• Riggs JE. Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy. Neurology. 1999 Apr 22;52(7):1517-8. doi: 10.1212/wnl.52.7.1517-a. No abstract available.
• Lambiase A, Rama P, Bonini S, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for corneal neurotrophic ulcers. N Engl J Med. 1998 Apr 23;338(17):1174-80. doi: 10.1056/NEJM199804233381702.
• Petty BG, Cornblath DR, Adornato BT, Chaudhry V, Flexner C, Wachsman M, Sinicropi D, Burton LE, Peroutka SJ. The effect of systemically administered recombinant human nerve growth factor in healthy human subjects. Ann Neurol. 1994 Aug;36(2):244-6. doi: 10.1002/ana.410360221.
• Zhou F, Wu P, Wang L, Wang HT, Zhang SB, Lin Y, Zhong H, Chen YH. The NGF point-injection for treatment of the sound-perceiving nerve deafness and tinnitus in 68 cases. J Tradit Chin Med. 2009 Mar;29(1):39-42. doi: 10.1016/s0254-6272(09)60029-7.
• Wu ZH, Huang J, Gao WH, Wang AL, Jia Q, Chen B, Xu S, Gu YH. [Effect of nerve growth factor on the promotion of sensory recovery of large skin graft in patients]. Zhonghua Shao Shang Za Zhi. 2007 Dec;23(6):440-3. Chinese.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2019
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (ACTUAL): May 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 24, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Alcohol-induced brain injury, atrophy, demyelination
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Neuroprotective Agents; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Free Radical Scavengers; Edaravone; Mitogens; Thiamine
• Other Study ID Numbers: 2019-13-NGF-EDV

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