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

Not Applicable

Completed

• Conditions: NASH (Non-Alcoholic Steatohepatitis)
• Interventions: Drug: Vitamin E softgel; Drug: Placebo

• Registration Number: NCT02962297
• Lead Sponsor: Zhejiang Medicine Co., Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-27
• Study First Submitted QC: 2016-11-10
• Study First Posted: 2016-11-11
• Study Start: 2016-12
• Status Verified: 2020-11
• Primary Completion: 2020-11-09
• Study Completion: 2021-12-17
• Last Update Submitted: 2023-03-30
• Last Update Posted: 2023-04-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
treatment group	Vitamin E softgel	Vitamin E softgel,100mg,Tid,orally, 96 weeks. All participants receive standardized recommendations for life-style modification (Diet modification, weight loss, exercise).
placebo group	Placebo	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).

Primary Outcome Measures

Name	Time	Method
Improvement in hepatic histology	after 96 weeks of treatment	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.

Trial Locations

Locations (15)

302 Military Hospital of China; 🇨🇳 Beijing, China

West China Hospital, Sichuan university; 🇨🇳 Chengdu, China

Guangdong Provincial Chinese Medicine Hospital; 🇨🇳 Guangzhou, China

Nanfang Hospital; 🇨🇳 Guangzhou, China

Beijing YouAn Hospital Capital Medical Univercity; 🇨🇳 Beijing, China

The First Hospital of China Medical University; 🇨🇳 Shenyang, China

Southwest Medical University Affiliated; 🇨🇳 Luzhou, China

The second people's Hospital of Tianjin; 🇨🇳 Tianjin, China

The First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhu, China

Beijing Ditan Hospital Capital Medical University; 🇨🇳 Beijin, Beijing, China

The first Affiliated Hospital, Sun Yat-sen University; 🇨🇳 Guangdong, China

The Affiliated Hospital of Hangzhou Normal University; 🇨🇳 Hangzhou, China

The Second Hospital of Nanjing; 🇨🇳 Nanjing, China

The First Affiliated Hospital of Medical University; 🇨🇳 Urumqi, China

General Hospital Ningxia Medical; 🇨🇳 Yinchuan, China