Clinical trial NCT02303730: Exenatide Compared With Insulin Glargine to Change Liver Fat Content in Type 2 Diabetes
Official title: Exenatide BID Compared With Insulin Glargine to Change Liver Fat Content in Non-alcoholic Fatty-liver Disease Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Non-alcoholic Fatty Liver Disease
Keywords: Diabetes
Non-alcoholic Fatty Liver Disease
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Huadong Hospital
name: Shanghai Minhang Central Hospital
name: Shanghai 6th People's Hospital
name: Shanghai Changzheng Hospital
First posted: 2014-12-01
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether exenatide is superior to insulin glargine (after 24 weeks) in reducing liver fat content (by MRS) in patients with newly diagnosed type 2 diabetes mellitus and concomitant non-alcoholic fatty-liver disease(NAFLD).

Detailed description: This is a randomized, open-label, parallel-group, active controlled, multi-center clinical trial to investigate whether exenatide is superior to insulin glargine in reducing liver fat content in patients with newly diagnosed type 2 diabetes mellitus and concomitant NAFLD.Patients with type 2 diabetes and concomitant NAFLD from 18-70 years of age, with inadequate glycaemic control defined as 7% ≤ HbA1c ≤ 10% and BMI≥24kg/ m2 at the time of screening. Patients should be on diet and exercise but drug treatment naive, no use of any glucagon-like peptide-1(GLP-1) analogues or insulin within 3 months before enrolment.Patients will have an screening period 2 weeks, and a 24-week open label treatment period.

All demographic data variables collected by descriptive analysis tests are used. Qualitative variables use absolute frequency and percentage, and numeric variables use average, mean, median, standard deviation, maximum, minimum, quartiles, etc. Unless specifically stated, statistical significance will be defined as P\<0.05 in the whole analysis procedure.For the primary endpoint of this study, superiority test will be applied to the quantitative data of these two groups. For secondary and exploratory efficacy variables, difference test will be used to analyse repeated measurement data from two groups. For essential Safety parameters, difference test will be used to analyse the differences between two groups.The analysis of all primary and secondary endpoints of efficacy and safety must be based on the Full Analysis Set (FAS). As supporting evidence, the analysis of primary endpoint variables must also comply with the Pre-protocol (PPS) Analysis.

Eligibility criteria: Inclusion Criteria:

* Male or female, 18 ≤ age ≤ 70 years old.
* Newly diagnosed type 2 diabetes mellitus (WHO Diagnostic criteria for diabetes mellitus, 1999).
* Patients with NAFLD, MRS measurement of liver fat content\> 10%.
* 7% ≤ HbA1c ≤ 10%
* No heavy drinking history within the last 5 years (alcohol intake: male \< 20 g/d, female \< 10 g/d)
* HBsAg (-), hepatitis C virus antibody (HCV-Ab) (-)
* BMI ≥ 24 kg/m2;

Exclusion Criteria:

* Pregnancy, lactation, intended pregnancy, or failure to take adequate contraceptive measures taken (contraception measures including sterilization, intrauterine device, oral contraceptives, and persistent use of condoms).
* Type 1 diabetes mellitus, gestational diabetes mellitus or other special types of diabetes.
* Liver and renal dysfunction (ALT or aspartate aminotransferase(AST) is 2.5 times higher than the upper limit of normal, or total bilirubin is 1.5 times higher than the upper limit of normal, or Cr ≥ 115 μmol/L).
* increased amylase (blood amylase is 2.5 times higher than the upper limit of normal) or presence of gastrointestinal disease.
* Use of drugs that may affect liver fat content within one month before or during the trial period, such as glucocorticoids, thyroid hormone, etc.
* Use of GLP-1 receptor agonist, dipeptidyl peptidase -4 (DPP-4) inhibitors or insulin within 3 months before enrolment
* Presence of serious dyslipidemia or other endocrine diseases (hypothyroidism, hypothalamic-pituitary dysfunction, etc).
* Fatty liver caused by viral hepatitis, drug, alcohol, Wilson disease or total parenteral nutrition.
* Presence of liver cancer, infection, biliary tract disease or recently increased liver enzyme due to medication.
* Participation in strenuous exercise or administration of any drugs that affect glucose metabolism.
* History of pancreatitis, alcohol abuse, metal disorders or history of allergy to investigational drug.
* Congestive heart failure defined as New York Heart Association (NYHA) class III or IV, unstable angina or myocardial infarction in recent 6 months.
* Any situation that may affect the implementation or results of the study.

Primary outcomes:
measure: Change in liver fat content（%） measured by MRS
timeFrame: baseline and 24 weeks
Secondary outcomes:
measure: Change in intra-abdominal visceral fat content (cm2), abdominal subcutaneous fat content (cm2), and ratio between intra-abdominal visceral fat and subcutaneous fat area by MRI
timeFrame: baseline and 24 weeks
measure: Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)
timeFrame: baseline and 24 weeks
measure: Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)
timeFrame: baseline and 24 weeks
measure: Change in body weight,waist circumference and hip circumference
timeFrame: baseline and 24 weeks
Other outcomes:
measure: Change in cardiac function measured by echocardiography
timeFrame: baseline and 24 weeks
measure: Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide)
timeFrame: baseline and 24 weeks
measure: Change in liver enzymes and laboratory parameters (hematology, biochemical tests)
timeFrame: baseline and 24 weeks
measure: Incidence of hypoglycaemia events
timeFrame: up to 24 weeks
measure: Incidence of adverse events（AEs）and Severe adverse events(SAEs)
timeFrame: up to 24 weeks
Locations:
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital
state: Shanghai
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism,Huadong Hospital
state: Shanghai
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xin Gao, doctor
role: PRINCIPAL_INVESTIGATOR
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