Vitamin E Versus Placebo for the Treatment of Non Diabetic Patients With Nonalcoholic Steatohepatitis

NCT02962297 | Completed

• 1 other identifier: VENS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 15

Brief Summary

VENS is a multicenter, randomized, double-masked, placebo parallel controlled trial to evaluate the efficacy and safety of treatment with vitamin E softgel in non diabetic adults with NASH compared to treatment with placebo in China.

Conditions

NASH (Non-Alcoholic Steatohepatitis)

Keywords

Vitamin E, Non Diabetic

Outcome Measures

Primary Outcomes (1)

• Improvement in hepatic histology

  Improvement in hepatic histology after 96 weeks of treatment as determined by liver biopsies compared to baseline. (Independent pathological evaluation committee was charged with interpreting of the histological characteristic and that allows for assessment of changes with therapy). The definition of histologic improvement requires all three of the following criteria: ① either improvement in NAS by at least 2 points or post-treatment NAS of 3 points or less, ② at least 1 point improvement in the score for ballooning or lobular inflammation③ no worsening of fibrosis stages.

  after 96 weeks of treatment

Study Arms (2)

treatment group

EXPERIMENTAL

Vitamin E softgel,100mg,Tid,orally, 96 weeks. All participants receive standardized recommendations for life-style modification (Diet modification, weight loss, exercise).

Drug: Vitamin E softgel

placebo group

PLACEBO COMPARATOR

A similar appearing placebo softgel , Vitamin E -Placebo, Tid, orally, 96 weeks, All participants receive standardized recommendations for life-style modification (Diet modification, weight loss, exercise).

Drug: Placebo

Interventions

Vitamin E softgel DRUG

All participants receive standardized recommendations for life-style modification (Diet modification, weight loss, exercise).

treatment group

Placebo DRUG

All participants receive standardized recommendations for life-style modification (Diet modification, weight loss, exercise). Height and weight, waist-to-hip ratio Review of diet and exercise

placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 -75, no limitation for ethnic and gender
• Body Mass Index(BMI) \< 35 kg/m2
• Patients with nonalcoholic steatohepatitis (NASH) based on liver biopsy obtained within 6 months before randomization. The histological evidence of NASH was defined as Non - alcoholic fatty liver disease activity score（NAS）≥ 4 (according to Nonalcoholic Steatohepatitis Clinical Research Network, NASH CRN) with a minimum 1 score for steatosis, lobular inflammation, and hepatocyte ballooning respectively.
• Fibrosis stage 0-3 according to nonalcoholic steatohepatitis clinical research network（NASH CRN).
• Without history of significant alcohol consumption for a period of more than 3 months within 5 years (\<10 g/day for female and \< 20 g/day for male).
• The lab test results should meet the requirements:
• ① Alanine aminotransferase （ALT） \< 5 times of normal upper limit
• ② Creatinine (Cr)\< normal upper limit
• ③ Albumin （ALB）\> 3.5g/L
• ④ International normalized ratio（INR）= 0.8-1.3
• ⑤ Fasting plasma glucose(FPG) \< 126mg/dL（7mmol/L） and/or 2h postprandial plasma glucose (PPG) \< 200mg/dL（11.1mmol/L）and/ or HbA1C \< 6.5 %
• If a participant with hypertension, he/she was required a stable antihypertensive drug(s) to keep blood pressure stable.(blood pressure \< 140/90 mmHg) 3 months prior to randomization.
• If a participant using a statin or fibrate, he/she was required on a stable dose to keep lipid stable (triglyceride(TG) \< 1.7 mmol/L, total cholesterol (TC) \< 5.72 mmol/L, LDL-c \< 3.64 mmol/L) 3 months prior to randomization.
• Women of childbearing potential: negative pregnancy test during screening or at randomization or willingness to use an effective form of birth control during the trial(at least include one barrier contraceptive method) and not breast feeding
• Men must agree to use an effective form of birth control during the trial(at least include one barrier contraceptive method)

You may not qualify if:

• Evidence of other form of acute or chronic liver disease. (Virus hepatitis, Hereditary hemochromatosis, Hepatolenticular degeneration, Alcoholic liver disease, Drug-induced hepatopathy).
• History of diabetic mellitus or use of antidiabetic drugs.
• Known heart failure of New York Heart Association class 2, 3, or 4.
• Wear of cardiac pacemaker.
• Hypothyroidism (TSH \> 2 times of upper normal limit).
• History of disease affecting drug absorption, distribution, metabolism (inflammatory bowel disease, gastrointestinal surgery, chronic pancreatitis, gluten allergy, vagotomy).
• Use of anti-NASH drugs within 3 months before randomization (metformin, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitor, glucagon-like peptide-1(GLP-1), sodium glucose contransporter2(SGLT2), S-adenosylmethionine -e(SAM-e), polyene phosphatidyl choline, glycyrrhizin, bicyclol, reduced glutathione, betaine, fish oil, silymarin,oberbic acid/ursodeoxycholic acid (OCA/UDCA), phosphodiesterase (PDE)-inhibitor, gemfibrozil, vitamin E, long term antibiotic (\>1 week).
• Positivity of antibody to Human Immunodeficiency Virus.
• Inability to safely obtain liver biopsy.
• Known intolerance to vitamin E
• Inability to fill out diary card, to manage diet and exercise, poor compliance.
• Dependence or abuse of alcohol and/or drugs.
• Any other condition which in the opinion of investigator would impede compliance or hinder completion of the study.

Sponsors & Collaborators

• Zhejiang Medicine Co., Ltd.: lead
• R&G Pharma Studies Co.,Ltd.: collaborator
• The Affiliated Hospital of Hangzhou Normal University: collaborator

Study Sites (15)

Beijing Ditan Hospital Capital Medical University

Beijin, Beijing Municipality, China

Location

302 Military Hospital of China

Beijing, China

Location

Beijing YouAn Hospital Capital Medical Univercity

Beijing, China

Location

West China Hospital, Sichuan university

Chengdu, China

Location

The first Affiliated Hospital, Sun Yat-sen University

Guangdong, China

Location

Guangdong Provincial Chinese Medicine Hospital

Guangzhou, China

Location

Nanfang Hospital

Guangzhou, China

Location

The Affiliated Hospital of Hangzhou Normal University

Hangzhou, China

Location

Southwest Medical University Affiliated

Luzhou, China

Location

The Second Hospital of Nanjing

Nanjing, China

Location

The First Hospital of China Medical University

Shenyang, China

Location

The second people's Hospital of Tianjin

Tianjin, China

Location

The First Affiliated Hospital of Medical University

Ürümqi, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhu, China

Location

General Hospital Ningxia Medical

Yinchuan, China

Location

Related Publications (2)

• Song Y, Ni W, Zheng M, Sheng H, Wang J, Xie S, Yang Y, Chi X, Chen J, He F, Fan X, Mi Y, Zhang J, Wang B, Bai L, Xie W, Zhong B, Yeo YH, Rui F, Zang S, Li J, Shi J; Chinese NAFLD Clinical Research Network (CNAFLD CRN). Vitamin E (300 mg) in the treatment of MASH: A multi-center, randomized, double-blind, placebo-controlled study. Cell Rep Med. 2025 Feb 18;6(2):101939. doi: 10.1016/j.xcrm.2025.101939.

  PMID: 39970876 DERIVED

• Zang S, Chen J, Song Y, Bai L, Chen J, Chi X, He F, Sheng H, Wang J, Xie S, Xie W, Yang Y, Zhang J, Zheng M, Zou Z, Wang B, Shi J; Chinese NAFLD Clinical Research Network (CNAFLD CRN). Haptoglobin Genotype and Vitamin E Versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis in China: A Multicenter, Randomized, Placebo-Controlled Trial Design. Adv Ther. 2018 Feb;35(2):218-231. doi: 10.1007/s12325-018-0670-8. Epub 2018 Feb 6.

  PMID: 29411270 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Junping Shi, Phd

  The Affiliated Hospital of Hangzhou Normal University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: November 11, 2016
• Study Start: December 1, 2016
• Primary Completion: November 9, 2020
• Study Completion: December 17, 2021
• Last Updated: April 3, 2023

Record last verified: 2020-11

Locations

CN (15)