Antidiabetic Effects on Intrahepatic Fat

• ClinicalTrials.gov Identifier: NCT03068065
• Recruitment Status: Completed
• First Posted: March 1, 2017
• Last Update Posted: March 1, 2017
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Information provided by (Responsible Party): Dalong Zhu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Tracking Information

• First Submitted Date: February 16, 2017
• First Posted Date: March 1, 2017
• Last Update Posted Date: March 1, 2017
• Actual Study Start Date: May 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2017)

Intrahepatic fat [ Time Frame: -7±3days; 168±3days ]

intrahepatic fat change from baseline by quantitative ultrasound

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 28, 2017)

• Liver function [ Time Frame: -7±3days; 28±3days; 84±3days; 168±3days ]
  serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST)
• Lipid [ Time Frame: -7±3days; 28±3days; 84±3days; 168±3days ]
  total cholesterol (CH), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL)
• Plasma glucose in standard meal tolerance test [ Time Frame: -7±3days; 168±3days ]
  plasma glucose was measured at 0, 30, 60, and 120 min after ingestion of the meal
• Plasma insulin in standard meal tolerance test [ Time Frame: -7±3days; 168±3days ]
  plasma insulin was measured at 0, 30, 60, and 120 min after ingestion of the meal
• Glucose control [ Time Frame: 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days ]
  fasting blood glucose (FBG), postprandial blood glucose (PBG)
• HbA1c [ Time Frame: -7±3days; 84±3days; 168±3days ]
  glycosylated hemoglobin A 1c (HbA1c) was measured by high-performance liquid chromatography
• Body composition [ Time Frame: -7±3days; 168±3days ]
  fat mass and lean tissue were measured by dual-energy X-ray absorptiometry
• Weight [ Time Frame: 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days ]
  body weight
• WC [ Time Frame: 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days ]
  waist circumference

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: February 28, 2017)

Number of Participants with gliclazide, liraglutide or metformin adverse events as a measure of safety and tolerability [ Time Frame: -7±3days; 0±3days; 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3day;168±3days ]

adverse events caused by the drugs

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Antidiabetic Effects on Intrahepatic Fat
• Official Title: Comparison of Efficacy of Liraglutide, Metformin and Gliclazide MR on Hepatic Lipid Content in Patients With Type 2 Diabetes (T2DM) and Non-alcoholic Fatty Liver (NAFLD)
• Brief Summary: This was a 24-week single-center, open-label, parallel controlled group comparing gliclazide, liraglutide, and metformin effects on diabetes with nonalcoholic fatty liver disease.
• Detailed Description: Following enrollment, eligible participants were randomized (1:1:1) using computer-generated random numbers to the metformin (Glucophage, Bristol-Myers Squibb), liraglutide (Victoza, Novo Nordisk), or gliclazide (Diamicron, Servier) groups. All patients were informed about a proper diet and exercise. For the metformin group (n = 31), the dosage was 250 mg thrice a day during the first week, 500 mg thrice a day during the second week, and 1000 mg twice a day from the third week to the conclusion of the study. For the gliclazide group (n = 31), the initial dosage was 30 mg before breakfast, which was gradually titrated to a maximum of 120 mg/day to achieve a fasting capillary plasma glucose of <7.0 mmol/L. For the liraglutide group (n = 31), the dosage was 0.6 mg/day during the first week, 1.2 mg/day during the second week, and 1.8 mg/day from the third week to the conclusion of the study.At the end of the study, data will be collected and analyzed.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Alcoholic Fatty Liver Disease
• Type2 Diabetes

Intervention

• Drug: Liraglutide
  the dosage of liraglutide was 0.6 mg/day during the first week, 1.2 mg/day during the second week, and 1.8 mg/day from the third week to the conclusion of the study
  Other Name: Victoza,Novo Nordisk
• Drug: Metformin
  the dosage of metformin was 250 mg thrice a day during the first week, 500 mg thrice a day during the second week, and 1000 mg twice a day from the third week to the conclusion of the study
  Other Name: Glucophage,Bristol-Myers Squibb
• Drug: Gliclazide
  the initial dosage of gliclazide was 30 mg before breakfast, which was gradually titrated to a maximum of 120 mg/day to achieve a fasting capillary plasma glucose of <7.0 mmol/L
  Other Name: Diamicron MR,Servier

Study Arms

• Active Comparator: Liraglutide
  the dosage of liraglutide was 0.6 mg/day during the first week, 1.2 mg/day during the second week, and 1.8 mg/day from the third week to the conclusion of the study
  Intervention: Drug: Liraglutide
• Active Comparator: Metformin
  the dosage of merformin was 250 mg thrice a day during the first week, 500 mg thrice a day during the second week, and 1000 mg twice a day from the third week to the conclusion of the study
  Intervention: Drug: Metformin
• Active Comparator: Gliclazide
  the initial dosage of gliclazide was 30 mg before breakfast, which was gradually titrated to a maximum of 120 mg/day to achieve a fasting capillary plasma glucose of <7.0 mmol/L
  Intervention: Drug: Gliclazide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2017): 87
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age: 18-70 years;
2. Type 2 diabetes mellitus;
3. Not used antidiabetic drugs within 3 months;
4. HbA1c(7-10%);
5. Presence of fatty liver disease (hepatic fat content ≥ 20% by quantitative ultrasonography);
6. Female subjects：post-menopausal women, take contraceptive measures three months before the test screening and can persist throughout the experimental period;
7. Body mass index (BMI) 20-35kg/m2, and stable Weight 3 months(less than 10% volatility);
8. patients signed the informed consent.

Exclusion Criteria:

1. Used antidiabetic drugs or any other possible hepatic steatosis associated with drugs within the past three months;
2. Suffering from pancreatitis or other pancreatic diseases or have other similar history;
3. GLP-1 analogs or sulfonylurea allergy history;
4. Liver dysfunction (aspartate aminotransferase ≥ 2.5 times of the normalupper limit);
5. Moderate to severe renal insufficiency (eGFR<60ml/min/1.73m2,calculated according to MDRD);
6. Female subjects drinking> 14 units / week; male subjects drinking> 21 units/week;
7. A history of metabolic or autoimmune liver diseases or viral hepatitis diseases;
8. A history of medullary thyroid carcinoma, multiple endocrine neoplasia 2 or family history;
9. Congestive heart failure (NYHA grade Ⅲ - Ⅳ grade);
10. Severe gastrointestinal diseases;
11. Other serious concomitant diseases;
12. Pregnant or planning pregnancy;
13. The researchers believe that the subjects with proliferative retinopathy or macular degeneration need urgentl treatment;
14. Subjects are using unknown ingredients or non herbal medicine preparations or local medicine, researchers believe that during the test the dose of traditional Chinese medicines can not be adjusted or disabled.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 17 Years to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03068065
• Other Study ID Numbers: ChiCTR-TRC-14004660
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Dalong Zhu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Study Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: Not Provided

Investigators

• Principal Investigator: Dalong Zhu, MD,PhD; the Affiliated Drum Tower Hospital of Nanjing University

• PRS Account: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Verification Date: February 2017