Clinical trial NCT02962297: Vitamin E Versus Placebo for the Treatment of Non Diabetic Patients With Nonalcoholic Steatohepatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NASH (Non-Alcoholic Steatohepatitis)
Keywords: Vitamin E, Non Diabetic
Lead sponsor: Zhejiang Medicine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: R&G Pharma Studies Co.,Ltd.
name: The Affiliated Hospital of Hangzhou Normal University
First posted: 2016-11-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age: 18 -75, no limitation for ethnic and gender
2. Body Mass Index(BMI) \< 35 kg/m2
3. 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.
4. Fibrosis stage 0-3 according to nonalcoholic steatohepatitis clinical research network（NASH CRN).
5. 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).
6. 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 %
7. 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.
8. 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.
9. 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
10. Men must agree to use an effective form of birth control during the trial(at least include one barrier contraceptive method)
11. All participants are needed to sign the informed consent form.

Exclusion Criteria:

1. Evidence of other form of acute or chronic liver disease. (Virus hepatitis, Hereditary hemochromatosis, Hepatolenticular degeneration, Alcoholic liver disease, Drug-induced hepatopathy).
2. History of diabetic mellitus or use of antidiabetic drugs.
3. Known heart failure of New York Heart Association class 2, 3, or 4.
4. Wear of cardiac pacemaker.
5. Hypothyroidism (TSH \> 2 times of upper normal limit).
6. History of disease affecting drug absorption, distribution, metabolism (inflammatory bowel disease, gastrointestinal surgery, chronic pancreatitis, gluten allergy, vagotomy).
7. 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).
8. Positivity of antibody to Human Immunodeficiency Virus.
9. Inability to safely obtain liver biopsy.
10. Known intolerance to vitamin E
11. Inability to fill out diary card, to manage diet and exercise, poor compliance.
12. Dependence or abuse of alcohol and/or drugs.
13. Any other condition which in the opinion of investigator would impede compliance or hinder completion of the study.

Primary outcomes:
measure: Improvement in hepatic histology
timeFrame: after 96 weeks of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Beijin
country: China
facility: Beijing Ditan Hospital Capital Medical University
state: Beijing
city: Beijing
country: China
facility: 302 Military Hospital of China
city: Beijing
country: China
facility: Beijing YouAn Hospital Capital Medical Univercity
city: Chengdu
country: China
facility: West China Hospital, Sichuan university
city: Guangdong
country: China
facility: The first Affiliated Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: Guangdong Provincial Chinese Medicine Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital
city: Hangzhou
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Luzhou
country: China
facility: Southwest Medical University Affiliated
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Tianjin
country: China
facility: The second people's Hospital of Tianjin
city: Urumqi
country: China
facility: The First Affiliated Hospital of Medical University
city: Wenzhu
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Yinchuan
country: China
facility: General Hospital Ningxia Medical
Study officials:
affiliation: The Affiliated Hospital of Hangzhou Normal University
name: Junping Shi, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.