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.

Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function.

Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function.

Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function.

Executive function by digit symbol substitute test (DSST) ranging from 0 to 90. Higher score indicates better executive function.

Cognitive assessment by Montreal Cognitive Assessment (MoCA) ranging from 0 to 30. Lower score indicates worse cognitive function.

Cognitive assessment by Montreal Cognitive Assessment (MoCA) ranging from 0 to 30. Lower score indicates worse cognitive function.

Craving assessment for alcohol by Obsessive Compulsive Drinking Scale (OCDS) ranging from 0 to 40. Higher score of OCDS indicates more desire for alcohol.

Psychological assessment by Generalized Anxiety Disorder-7 (GAD-7) ranging from 0 to 21. Higher score indicates more severer anxiety.

Psychological assessment by Patient Health Questionnaire-9 (PHQ-9) ranging from 0 to 27. Higher score indicates more severer depression.

Psychological assessment by Pittsburgh Sleep Quality Index (PSQI) ranging from 0 to 21. Higher score indicates worse sleep.

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

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.

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.

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.