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

This study is currently recruiting participants.
Verified February 2016 by Xin Gao, Fudan University
Sponsor:
ClinicalTrials.gov Identifier:
NCT01720719
First Posted: November 2, 2012
Last Update Posted: February 3, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Pfizer
Information provided by (Responsible Party):
Xin Gao, Fudan University
  Purpose
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.

Condition Intervention Phase
Fatty Liver Dyslipidemias Diabetes Mellitus Drug: atorvastatin Drug: Vitamin E Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Xin Gao, Fudan University:

Primary Outcome Measures:
  • Liver fat content(%) [ Time Frame: 24 weeks ]
    MRS (magnetic resonance spectroscopy analysis): liver fat content (%).


Secondary Outcome Measures:
  • Abdominal visceral fat area(cm2) [ Time Frame: 24 weeks ]
    MRI (magnetic resonance imaging): abdominal visceral fat area (cm2)

  • Abdominal subcutaneous fat area(cm2) [ Time Frame: 24 weeks ]
    MRI(Magnetic Resonance Imaging):abdominal subcutaneous fat content (cm2)

  • Lipid profiles [ Time Frame: 24 weeks ]
    lipid profiles (total cholesterol, HDL-C, LDL-C, very low density lipoprotein and free fatty acids)

  • Liver enzymes [ Time Frame: 24 weeks ]
    liver enzymes (Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Gamma-glutamyl transferase(GGT))

  • Glucose metabolism [ Time Frame: 24 weeks ]
    fasting plasma glucose(FPG), postprandial plasma glucose(PPG), HbA1c, fasting C-peptide and 2-hour postprandial C-peptide

  • Body weight [ Time Frame: 24 weeks ]
    Body weight

  • Anthropometric test [ Time Frame: 24 weeks ]
    waist and hip circumferences

  • Muscle enzymes [ Time Frame: 24 weeks ]
    MM isoenzyme of creatine kinase(CK-MM), MB isoenzyme of creatine kinase(CK-MB)


Estimated Enrollment: 120
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Vitamin E
Oral Vitamin E 300mg, qd, for 24 weeks
Drug: Vitamin E
Oral Vitamin E 300mg, qd, for 24 weeks
Experimental: Atorvastatin
Oral atorvastatin 20mg, qd, for 24 weeks
Drug: atorvastatin
Oral atorvastatin 20mg, qd, for 24 weeks

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01720719


Contacts
Contact: Xin Gao, doctor 862164041990 ext 8021 gao.xin@zs-hospital.sh.cn; happy20061208@126.com
Contact: Hongmei Yan, doctor 13761666976 yan.hongmei@zs-hospital.sh.cn

Locations
China, Shanghai
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University Recruiting
Shanghai, Shanghai, China, 200032
Contact: Xin Gao, doctor    862164041990 ext 8021    gao.xin@zs-hospital.sh.cn   
Contact: Hongmei Yan, doctor    13761666976    yan.hongmei@zs-hospital.sh.cn   
Principal Investigator: Xin Gao, doctor         
Sub-Investigator: hongmei Yan, doctor         
Sub-Investigator: Mingfeng Xia, doctor         
Sponsors and Collaborators
Xin Gao
Pfizer
Investigators
Principal Investigator: Xin Gao, doctor Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
  More Information

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Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB Jr, Kempf J, Zinman B, Haffner SM; insulin resistance atherosclerosis study. Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes. 2004 Oct;53(10):2623-32.
Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21.
Mehta SR, Thomas EL, Patel N, Crofton ME, McCarthy J, Eliahoo J, Morin SX, Fitzpatrick J, Durighel G, Goldstone AP, Johnston DG, Bell JD, Taylor-Robinson SD. Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification. Hepatol Res. 2010 Apr;40(4):399-406. doi: 10.1111/j.1872-034X.2009.00620.x. Epub 2010 Mar 4.
Argo CK, Loria P, Caldwell SH, Lonardo A. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology. 2008 Aug;48(2):662-9. doi: 10.1002/hep.22402. Review.
Hyogo H, Tazuma S, Arihiro K, Iwamoto K, Nabeshima Y, Inoue M, Ishitobi T, Nonaka M, Chayama K. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism. 2008 Dec;57(12):1711-8. doi: 10.1016/j.metabol.2008.07.030.
Kiyici M, Gulten M, Gurel S, Nak SG, Dolar E, Savci G, Adim SB, Yerci O, Memik F. Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis. Can J Gastroenterol. 2003 Dec;17(12):713-8.
Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis. 2004 May;174(1):193-6.
Hatzitolios A, Savopoulos C, Lazaraki G, Sidiropoulos I, Haritanti P, Lefkopoulos A, Karagiannopoulou G, Tzioufa V, Dimitrios K. Efficacy of omega-3 fatty acids, atorvastatin and orlistat in non-alcoholic fatty liver disease with dyslipidemia. Indian J Gastroenterol. 2004 Jul-Aug;23(4):131-4.
Gómez-Domínguez E, Gisbert JP, Moreno-Monteagudo JA, García-Buey L, Moreno-Otero R. A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1643-7.
Antonopoulos S, Mikros S, Mylonopoulou M, Kokkoris S, Giannoulis G. Rosuvastatin as a novel treatment of non-alcoholic fatty liver disease in hyperlipidemic patients. Atherosclerosis. 2006 Jan;184(1):233-4. Epub 2005 Oct 5.
Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol. 2011 Jan;106(1):71-7. doi: 10.1038/ajg.2010.299. Epub 2010 Sep 14.
Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K, Pagourelias ED, Theocharidou E, Karagiannis A, Mikhailidis DP; GREACE Study Collaborative Group. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet. 2010 Dec 4;376(9756):1916-22. doi: 10.1016/S0140-6736(10)61272-X. Epub 2010 Nov 23.
Wiesinger HA, Shah J, White A, Yoshida EM, Frohlich J, Sirrs S, Gill S, Byrne MF. Liver biochemistry abnormalities in a quaternary care lipid clinic database. Ann Hepatol. 2008 Jan-Mar;7(1):63-6.
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Responsible Party: Xin Gao, Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
ClinicalTrials.gov Identifier: NCT01720719     History of Changes
Other Study ID Numbers: WS2334187
First Submitted: October 31, 2012
First Posted: November 2, 2012
Last Update Posted: February 3, 2016
Last Verified: February 2016

Keywords provided by Xin Gao, Fudan University:
Non-alcoholic Fatty Liver Disease
Dyslipidemias
Diabetes Mellitus
atorvastatin
Vitamin E

Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Liver Diseases
Dyslipidemias
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Lipid Metabolism Disorders
Vitamins
Vitamin E
Tocopherols
Tocotrienols
alpha-Tocopherol
Atorvastatin Calcium
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antioxidants
Protective Agents


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