<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01720719</url>
  </required_header>
  <id_info>
    <org_study_id>WS2334187</org_study_id>
    <nct_id>NCT01720719</nct_id>
  </id_info>
  <brief_title>Atorvastatin Versus Vitamin E in Treatment of Non-alcoholic Fatty Liver Disease</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xin Gao</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Fudan University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to compare the impact of atorvastatin 20mg qd and Vitamin E 300mg&#xD;
      qd therapy on liver fat content in patients with type 2 diabetes associated with high LDL-C&#xD;
      and non-alcoholic fatty liver disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Previous studies have preliminary proven the safety and efficacy of atorvastatin tablets in&#xD;
      the treatment of Non-alcoholic fatty liver disease (NAFLD).However, the sample size of these&#xD;
      studies is small and most studies use B-ultrasound or CT for semi-quantitative determination&#xD;
      of liver fat content. The defects of evaluation methods seriously affect the accuracy of the&#xD;
      studies. Also, antioxidant agents have been proposed as a potentially effective treatment.&#xD;
      Vitamin E is a potent antioxidant compound, which has been tested in pediatric NAFLD because&#xD;
      of the absence of side effects. Conflicting results have been reported in clinical trials,&#xD;
      both in children and in adults. The project intends to adopt advanced proton magnetic&#xD;
      resonance spectroscopy (1H-MRS) to non-invasively and precisely determine liver fat content&#xD;
      and understand the change in liver fat content before and after the treatment with&#xD;
      atorvastatin tablets or Vitamin E in NAFLD patients with abnormal lipid metabolism and type 2&#xD;
      diabetes. We also intend to compare the therapeutic effects of atorvastatin and Vitamin E in&#xD;
      the treatment of NAFLD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2013</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver fat content(%)</measure>
    <time_frame>24 weeks</time_frame>
    <description>MRS (magnetic resonance spectroscopy analysis): liver fat content (%).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Abdominal visceral fat area(cm2)</measure>
    <time_frame>24 weeks</time_frame>
    <description>MRI (magnetic resonance imaging): abdominal visceral fat area (cm2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Abdominal subcutaneous fat area(cm2)</measure>
    <time_frame>24 weeks</time_frame>
    <description>MRI(Magnetic Resonance Imaging):abdominal subcutaneous fat content (cm2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid profiles</measure>
    <time_frame>24 weeks</time_frame>
    <description>lipid profiles (total cholesterol, HDL-C, LDL-C, very low density lipoprotein and free fatty acids)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver enzymes</measure>
    <time_frame>24 weeks</time_frame>
    <description>liver enzymes (Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Gamma-glutamyl transferase(GGT))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose metabolism</measure>
    <time_frame>24 weeks</time_frame>
    <description>fasting plasma glucose(FPG), postprandial plasma glucose(PPG), HbA1c, fasting C-peptide and 2-hour postprandial C-peptide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body weight</measure>
    <time_frame>24 weeks</time_frame>
    <description>Body weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometric test</measure>
    <time_frame>24 weeks</time_frame>
    <description>waist and hip circumferences</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle enzymes</measure>
    <time_frame>24 weeks</time_frame>
    <description>MM isoenzyme of creatine kinase(CK-MM), MB isoenzyme of creatine kinase(CK-MB)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Fatty Liver</condition>
  <condition>Dyslipidemias</condition>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Vitamin E</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral Vitamin E 300mg, qd, for 24 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atorvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral atorvastatin 20mg, qd, for 24 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>atorvastatin</intervention_name>
    <description>Oral atorvastatin 20mg, qd, for 24 weeks</description>
    <arm_group_label>Atorvastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin E</intervention_name>
    <description>Oral Vitamin E 300mg, qd, for 24 weeks</description>
    <arm_group_label>Vitamin E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Sign informed consent before involvement in any trial-related activity (trial-related&#xD;
             activity refers to measures that will not be adopted during the normal treatment of&#xD;
             patients).&#xD;
&#xD;
          2. Male or female, 18 years ≤ age ≤ 70 years.&#xD;
&#xD;
          3. Type 2 diabetes (already diagnosed or oral glucose tolerance test(OGTT) tested and&#xD;
             found complying with the 2003 ADA diagnostic criteria for diabetes).&#xD;
&#xD;
          4. Patients with non-alcoholic fatty liver disease, MRS measurement of liver fat content&gt;&#xD;
             10%.&#xD;
&#xD;
          5. Without taking any lipid-lowering drugs or Vitamin E in 3 months before enrollment.&#xD;
&#xD;
          6. LDL-C ≥ 2.6mmol/L.&#xD;
&#xD;
          7. No heavy drinking history (alcohol intake: male &lt; 20g/d, female &lt; 10g/d).&#xD;
&#xD;
          8. HBsAg (-), HCV-Ab (-).&#xD;
&#xD;
          9. 18.5 kg/m2 ≤ BMI ≤ 40kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Liver, renal dysfunction (ALT or AST is 2.5 times higher than the upper limit of&#xD;
             normal, or total bilirubin(TB) is 1.5 times higher than the upper limit of normal, or&#xD;
             Cr ≥ 115μmol/L).&#xD;
&#xD;
          2. Muscle enzyme is 2 times higher than normal.&#xD;
&#xD;
          3. Type 1 diabetes, gestational diabetes, or other special types of diabetes.&#xD;
&#xD;
          4. Has not used drugs that may affect the liver fat content, such as glucocorticoids and&#xD;
             thyroxine within one month before and during the trial.&#xD;
&#xD;
          5. With hypothyroidism, hypothalamic-pituitary dysfunction, sleep apnea syndrome,&#xD;
             acanthosis nigricans, polycystic ovary syndrome, psoriasis, colorectal adenomas polyps&#xD;
             and other diseases that NAFLD is easily associated with.&#xD;
&#xD;
          6. Previous history of chronic viral hepatitis, autoimmune liver disease, drug-induced&#xD;
             liver disease and other liver diseases caused by genetic factors.&#xD;
&#xD;
          7. Severe uncontrolled hypertension (treated, sitting resting systolic blood pressure ≥&#xD;
             180 mmHg and/or diastolic blood pressure ≥ 100mmHg).&#xD;
&#xD;
          8. Pregnancy, breastfeeding, planned pregnancy, or failure to take adequate contraceptive&#xD;
             measures (contraception measures include sterilization, intrauterine device(IUD), oral&#xD;
             contraceptives and consistent condom use).&#xD;
&#xD;
          9. With intellectual, psychological or language barriers, so that the subjects cannot&#xD;
             fully understand or cooperate with the study.&#xD;
&#xD;
         10. Any circumstances that may affect the implementation or results of the study.&#xD;
&#xD;
         11. Class III or Class IV heart disease by New York Heart Association(NYHA)&#xD;
             classification, unstable angina or attack of myocardial infarction in recent 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xin Gao, doctor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Xin Gao, doctor</last_name>
    <phone>862164041990</phone>
    <phone_ext>8021</phone_ext>
    <email>gao.xin@zs-hospital.sh.cn; happy20061208@126.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Hongmei Yan, doctor</last_name>
    <phone>13761666976</phone>
    <email>yan.hongmei@zs-hospital.sh.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xin Gao, doctor</last_name>
      <phone>862164041990</phone>
      <phone_ext>8021</phone_ext>
      <email>gao.xin@zs-hospital.sh.cn</email>
    </contact>
    <contact_backup>
      <last_name>Hongmei Yan, doctor</last_name>
      <phone>13761666976</phone>
      <email>yan.hongmei@zs-hospital.sh.cn</email>
    </contact_backup>
    <investigator>
      <last_name>Xin Gao, doctor</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>hongmei Yan, doctor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mingfeng Xia, doctor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
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    <citation>Fujimoto WY, Bergstrom RW, Boyko EJ, Chen KW, Leonetti DL, Newell-Morris L, Shofer JB, Wahl PW. Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study. Diabetes Care. 1999 Nov;22(11):1808-12. doi: 10.2337/diacare.22.11.1808.</citation>
    <PMID>10546012</PMID>
  </reference>
  <reference>
    <citation>Ye Y, Bao Y, Hou X, Pan X, Wu H, Li H, Wang C, Tang J, Lu H, Xiang K, Jia W. Identification of waist circumference cutoffs for abdominal obesity in the Chinese population: a 7.8-year follow-up study in the Shanghai urban area. Int J Obes (Lond). 2009 Sep;33(9):1058-62. doi: 10.1038/ijo.2009.134. Epub 2009 Jul 7.</citation>
    <PMID>19581913</PMID>
  </reference>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>October 31, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <last_update_submitted>February 2, 2016</last_update_submitted>
  <last_update_submitted_qc>February 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 3, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Xin Gao</investigator_full_name>
    <investigator_title>Department of Endocrinology and Metabolism, Zhongshan Hospital</investigator_title>
  </responsible_party>
  <keyword>Non-alcoholic Fatty Liver Disease</keyword>
  <keyword>Dyslipidemias</keyword>
  <keyword>Diabetes Mellitus</keyword>
  <keyword>atorvastatin</keyword>
  <keyword>Vitamin E</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin E</mesh_term>
    <mesh_term>Atorvastatin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01720719
org study id: WS2334187
nct id: NCT01720719
lead sponsor: 
collaborator: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Liver fat content(%)
time frame: 24 weeks
description: MRS (magnetic resonance spectroscopy analysis): liver fat content (%).
measure: Abdominal visceral fat area(cm2)
time frame: 24 weeks
description: MRI (magnetic resonance imaging): abdominal visceral fat area (cm2)
measure: Abdominal subcutaneous fat area(cm2)
time frame: 24 weeks
description: MRI(Magnetic Resonance Imaging):abdominal subcutaneous fat content (cm2)
measure: Lipid profiles
time frame: 24 weeks
description: lipid profiles (total cholesterol, HDL-C, LDL-C, very low density lipoprotein and free fatty acids)
measure: Liver enzymes
time frame: 24 weeks
description: liver enzymes (Alanine aminotransferase(ALT), Aspartate aminotransferase(AST), Gamma-glutamyl transferase(GGT))
measure: Glucose metabolism
time frame: 24 weeks
description: fasting plasma glucose(FPG), postprandial plasma glucose(PPG), HbA1c, fasting C-peptide and 2-hour postprandial C-peptide
measure: Body weight
time frame: 24 weeks
description: Body weight
measure: Anthropometric test
time frame: 24 weeks
description: waist and hip circumferences
measure: Muscle enzymes
time frame: 24 weeks
description: MM isoenzyme of creatine kinase(CK-MM), MB isoenzyme of creatine kinase(CK-MB)
arm group label: Vitamin E
arm group type: Active Comparator
description: Oral Vitamin E 300mg, qd, for 24 weeks
arm group label: Atorvastatin
arm group type: Experimental
description: Oral atorvastatin 20mg, qd, for 24 weeks
intervention type: Drug
intervention name: atorvastatin
description: Oral atorvastatin 20mg, qd, for 24 weeks
arm group label: Atorvastatin
intervention type: Drug
intervention name: Vitamin E
description: Oral Vitamin E 300mg, qd, for 24 weeks
arm group label: Vitamin E
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Xin Gao, doctor
role: Principal Investigator
affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
last name: Xin Gao, doctor
phone: 862164041990
phone ext: 8021
email: gao.xin@zs-hospital.sh.cn; happy20061208@126.com
last name: Hongmei Yan, doctor
phone: 13761666976
email: yan.hongmei@zs-hospital.sh.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: China
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responsible party type: Sponsor-Investigator
investigator affiliation: Fudan University
investigator full name: Xin Gao
investigator title: Department of Endocrinology and Metabolism, Zhongshan Hospital
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Diabetes Mellitus
mesh term: Dyslipidemias
mesh term: Vitamin E
mesh term: Atorvastatin