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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Randomized Open Label Trial on the Impact of 24 Weeks of Atorvastatin Therapy on Liver Fat Content and Abdominal Fat Content in Patients With Type 2 Diabetes Combined With High LDL-C and Non-alcoholic Fatty Liver Disease

Conditions
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Fatty Liver, Dyslipidemias, Diabetes Mellitus

Intervention / Treatment
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* Drug: atorvastatin
* Drug: Vitamin E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Male or female, 18 years ≤ age ≤ 70 years. Type 2 diabetes (already diagnosed or oral glucose tolerance test(OGTT) tested and found complying with the 2003 ADA diagnostic criteria for diabetes). Patients with non-alcoholic fatty liver disease, MRS measurement of liver fat content> 10%. Without taking any lipid-lowering drugs or Vitamin E in 3 months before enrollment. LDL-C ≥ 2.6mmol/L. No heavy drinking history (alcohol intake: male < 20g/d, female < 10g/d). HBsAg (-), HCV-Ab (-). 18.5 kg/m2 ≤ BMI ≤ 40kg/m2 Exclusion Criteria: 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). Muscle enzyme is 2 times higher than normal. Type 1 diabetes, gestational diabetes, or other special types of diabetes. Has not used drugs that may affect the liver fat content, such as glucocorticoids and thyroxine within one month before and during the trial. 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. Previous history of chronic viral hepatitis, autoimmune liver disease, drug-induced liver disease and other liver diseases caused by genetic factors. Severe uncontrolled hypertension (treated, sitting resting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100mmHg). Pregnancy, breastfeeding, planned pregnancy, or failure to take adequate contraceptive measures (contraception measures include sterilization, intrauterine device(IUD), oral contraceptives and consistent condom use). With intellectual, psychological or language barriers, so that the subjects cannot fully understand or cooperate with the study. Any circumstances that may affect the implementation or results of the study. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin E<br>Oral Vitamin E 300mg, qd, for 24 weeks | Drug: Vitamin E<br>* Oral Vitamin E 300mg, qd, for 24 weeks<br>|
| Experimental: Atorvastatin<br>Oral atorvastatin 20mg, qd, for 24 weeks | Drug: atorvastatin<br>* Oral atorvastatin 20mg, qd, for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver fat content(%) | MRS (magnetic resonance spectroscopy analysis): liver fat content (%). | 24 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic Fatty Liver Disease, Dyslipidemias, Diabetes Mellitus, atorvastatin, Vitamin E