Atorvastatin Versus Vitamin E in Treatment of Non-alcoholic Fatty Liver Disease

Phase 4

• Conditions: Diabetes Mellitus; Dyslipidemias; Fatty Liver
• Interventions: Drug: atorvastatin; Drug: Vitamin E

• Registration Number: NCT01720719
• Lead Sponsor: Xin Gao

Brief Summary

The purpose of the study is to compare the impact of atorvastatin 20mg qd and Vitamin E 300mg qd therapy on liver fat content in patients with type 2 diabetes associated with high LDL-C and non-alcoholic fatty liver disease.

Detailed Description

Previous studies have preliminary proven the safety and efficacy of atorvastatin tablets in the treatment of Non-alcoholic fatty liver disease (NAFLD).However, the sample size of these studies is small and most studies use B-ultrasound or CT for semi-quantitative determination of liver fat content. The defects of evaluation methods seriously affect the accuracy of the studies. Also, antioxidant agents have been proposed as a potentially effective treatment. Vitamin E is a potent antioxidant compound, which has been tested in pediatric NAFLD because of the absence of side effects. Conflicting results have been reported in clinical trials, both in children and in adults. The project intends to adopt advanced proton magnetic resonance spectroscopy (1H-MRS) to non-invasively and precisely determine liver fat content and understand the change in liver fat content before and after the treatment with atorvastatin tablets or Vitamin E in NAFLD patients with abnormal lipid metabolism and type 2 diabetes. We also intend to compare the therapeutic effects of atorvastatin and Vitamin E in the treatment of NAFLD.

Study Timeline

• Study First Submitted: 2012-10-31
• Study First Submitted QC: 2012-11-01
• Study First Posted: 2012-11-02
• Study Start: 2013-05
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-02
• Last Update Posted: 2016-02-03
• Primary Completion: 2016-12
• Study Completion: 2016-12

Recruitment & Eligibility

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

Inclusion Criteria

1. Sign informed consent before involvement in any trial-related activity (trial-related activity refers to measures that will not be adopted during the normal treatment of patients).
2. Male or female, 18 years ≤ age ≤ 70 years.
3. Type 2 diabetes (already diagnosed or oral glucose tolerance test(OGTT) tested and found complying with the 2003 ADA diagnostic criteria for diabetes).
4. Patients with non-alcoholic fatty liver disease, MRS measurement of liver fat content> 10%.
5. Without taking any lipid-lowering drugs or Vitamin E in 3 months before enrollment.
6. LDL-C ≥ 2.6mmol/L.
7. No heavy drinking history (alcohol intake: male < 20g/d, female < 10g/d).
8. HBsAg (-), HCV-Ab (-).
9. 18.5 kg/m2 ≤ BMI ≤ 40kg/m2

Exclusion Criteria

1. Liver, renal dysfunction (ALT or AST is 2.5 times higher than the upper limit of normal, or total bilirubin(TB) is 1.5 times higher than the upper limit of normal, or Cr ≥ 115μmol/L).
2. Muscle enzyme is 2 times higher than normal.
3. Type 1 diabetes, gestational diabetes, or other special types of diabetes.
4. Has not used drugs that may affect the liver fat content, such as glucocorticoids and thyroxine within one month before and during the trial.
5. With hypothyroidism, hypothalamic-pituitary dysfunction, sleep apnea syndrome, acanthosis nigricans, polycystic ovary syndrome, psoriasis, colorectal adenomas polyps and other diseases that NAFLD is easily associated with.
6. Previous history of chronic viral hepatitis, autoimmune liver disease, drug-induced liver disease and other liver diseases caused by genetic factors.
7. Severe uncontrolled hypertension (treated, sitting resting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100mmHg).
8. Pregnancy, breastfeeding, planned pregnancy, or failure to take adequate contraceptive measures (contraception measures include sterilization, intrauterine device(IUD), oral contraceptives and consistent condom use).
9. With intellectual, psychological or language barriers, so that the subjects cannot fully understand or cooperate with the study.
10. Any circumstances that may affect the implementation or results of the study.
11. Class III or Class IV heart disease by New York Heart Association(NYHA) classification, unstable angina or attack of myocardial infarction in recent 6 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atorvastatin	atorvastatin	Oral atorvastatin 20mg, qd, for 24 weeks
Vitamin E	Vitamin E	Oral Vitamin E 300mg, qd, for 24 weeks

Primary Outcome Measures

Name	Time	Method
Liver fat content(%)	24 weeks	MRS (magnetic resonance spectroscopy analysis): liver fat content (%).

Secondary Outcome Measures

Name	Time	Method
Abdominal visceral fat area(cm2)	24 weeks	MRI (magnetic resonance imaging): abdominal visceral fat area (cm2)
Body weight	24 weeks	Body weight
Abdominal subcutaneous fat area(cm2)	24 weeks	MRI(Magnetic Resonance Imaging):abdominal subcutaneous fat content (cm2)
Lipid profiles	24 weeks	lipid profiles (total cholesterol, HDL-C, LDL-C, very low density lipoprotein and free fatty acids)
Liver enzymes	24 weeks	liver enzymes (Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Gamma-glutamyl transferase(GGT))
Glucose metabolism	24 weeks	fasting plasma glucose(FPG), postprandial plasma glucose(PPG), HbA1c, fasting C-peptide and 2-hour postprandial C-peptide
Anthropometric test	24 weeks	waist and hip circumferences
Muscle enzymes	24 weeks	MM isoenzyme of creatine kinase(CK-MM), MB isoenzyme of creatine kinase(CK-MB)

Trial Locations

Locations (1)

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China