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

NCT03968042 | Unknown Phase 2

• 1 other identifier: 2019-13-NGF-EDV
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alcohol-induced Brain Injury

Keywords

Alcohol-induced brain injury, atrophy, demyelination

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (7)

• The rate of relapse of alcohol dependence after discharge from hospital

  2 months

• Duration of abstinence

  6 months

• Alcohol intake

  2 weeks, 2 months, 3 months, 6 months

• Craving for alcohol

  2 weeks, 2 months, 3 months, 6 months

• Psychological assessment - Anxiety

  2 weeks, 2 months, 3 months, 6 months

Study Arms (3)

Regular treatment (RT)

PLACEBO COMPARATOR

Combination of vitamin B1, B6, C, E and mecobalamine

Drug: Combination of vitamin B1, B6, C, E and mecobalamine

RT with NGF

EXPERIMENTAL

Nerve growth factor adding to regular treatment

Drug: Nerve Growth Factor; Drug: Combination of vitamin B1, B6, C, E and mecobalamine

RT with EDV

EXPERIMENTAL

Edaravone adding to regular treatment

Drug: Edaravone; Drug: Combination of vitamin B1, B6, C, E and mecobalamine

Interventions

Nerve Growth Factor DRUG

Intramuscular injection for 2 weeks

RT with NGF

Edaravone DRUG

Intravenous injection for 2 weeks

RT with EDV

Combination of vitamin B1, B6, C, E and mecobalamine DRUG

Medications of combination of vitamin B1, B6, C, E and mecobalamine for 6 months

RT with EDV; RT with NGF; Regular treatment (RT)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

RECRUITING

Related Publications (12)

• 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.

  PMID: 26060244 BACKGROUND

• 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.

  PMID: 24135530 BACKGROUND

• 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.

  PMID: 19240603 BACKGROUND

• 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.

  PMID: 28522181 BACKGROUND

• 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.

  PMID: 9748012 BACKGROUND

• 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.

  PMID: 10227655 BACKGROUND

• 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.

  PMID: 10720278 BACKGROUND

• 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.

  PMID: 9554857 BACKGROUND

• 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.

  PMID: 8053664 BACKGROUND

• 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.

  PMID: 19514187 BACKGROUND

• 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.

  PMID: 18457257 BACKGROUND

• Wang H, Liu L, Zhou X, Guan Y, Li Y, Chen P, Duan R, Yang W, Rong X, Wu C, Yang J, Yang M, Jia Y, Hu J, Zhu X, Peng Y. Efficacy and safety of short-term edaravone or nerve growth factor add-on therapy for alcohol-related brain damage: A multi-centre randomised control trial. Addiction. 2024 Apr;119(4):717-729. doi: 10.1111/add.16398. Epub 2023 Dec 4.

  PMID: 38049955 DERIVED

MeSH Terms

Conditions

Atrophy; Demyelinating Diseases

Interventions

Nerve Growth Factor; Edaravone

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Nerve Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Nerve Tissue Proteins; Biological Factors; Antipyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Ying Peng, MD, PhD

CONTACT

+86-13380051581; pengy2@mail.sysu.edu.cn

Hongxuan Wang, MD, PhD

CONTACT

+86-13824498978; wanghx8@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director of Department of Neurology

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: May 30, 2019
• Study Start: June 30, 2019
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: October 27, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)