Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exenatide Compared With Insulin Glargine to Change Liver Fat Content in Type 2 Diabetes

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02303730
Recruitment Status : Completed
First Posted : December 1, 2014
Last Update Posted : August 28, 2019
Sponsor:
Collaborators:
Huadong Hospital
Shanghai Minhang Central Hospital
Shanghai 6th People's Hospital
Shanghai Changzheng Hospital
Information provided by (Responsible Party):
Xin Gao, Fudan University

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).

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Non-alcoholic Fatty Liver Disease Drug: Exenatide Drug: insulin glargine Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2015
Actual Primary Completion Date : November 2017
Actual Study Completion Date : November 2017


Arm Intervention/treatment
Experimental: Exenatide
Exenatide 5 ug twice daily 1 hour before meal subcutaneously for 4 weeks, then add to 10 ug twice daily 1 hour before meal subcutaneously for another 20 weeks
Drug: Exenatide
The starting dose of exenatide is 5 ug bid, subcutaneously, for 4 weeks, followed by 10 ug bid, subcutaneously, for 20 weeks. If hypoglycaemia (blood glucose<2.9 mmol/l or < 3.9 mmol/l at least 2 times) or serious intolerance occurs, the dose will be adjusted to 5 ug bid, subcutaneously.
Other Name: Byetta

Active Comparator: Insulin glargine
Insulin glargine subcutaneously, once daily, for 24 weeks
Drug: insulin glargine

The starting dose of insulin glargine will depend upon the HbA1c level at screening(HbA1c <8% use 0.1 -0.2 U/kg per day;HbA1c >8% use 0.2 -0.3 U/kg per day).

Dose adjustment protocol for insulin glargine (at least 3 determinations of fasting blood glucose per week):

fasting blood glucose(FBG) > 180 mg/dL(10 mmol/l): add 4 U; FBG 140-180 mg/dL(7.8-10 mmol/l): add 2 U; FBG 126-139 mg/dL(7.0-7.8 mmol/l): add 1 U.

If hypoglycemia, reduce insulin glargine by:

blood glucose <70mg/dl(3.9mmol/l): 10%-20%; blood glucose <40mg/dl(2.2mmol/l): 20%-40%.

Other Name: Lantus




Primary Outcome Measures :
  1. Change in liver fat content(%) measured by MRS [ Time Frame: baseline and 24 weeks ]
    Change in liver fat content(%) measured by MRS


Secondary Outcome Measures :
  1. 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 [ Time Frame: baseline and 24 weeks ]
    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

  2. Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c) [ Time Frame: baseline and 24 weeks ]
    Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)

  3. Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL) [ Time Frame: baseline and 24 weeks ]
    Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)

  4. Change in body weight,waist circumference and hip circumference [ Time Frame: baseline and 24 weeks ]
    Change in body weight,waist circumference and hip circumference


Other Outcome Measures:
  1. Change in cardiac function measured by echocardiography [ Time Frame: baseline and 24 weeks ]
    Change in cardiac function measured by echocardiography

  2. Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide) [ Time Frame: baseline and 24 weeks ]
    Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide)

  3. Change in liver enzymes and laboratory parameters (hematology, biochemical tests) [ Time Frame: baseline and 24 weeks ]
    Change in liver enzymes and laboratory parameters (hematology, biochemical tests)

  4. Incidence of hypoglycaemia events [ Time Frame: up to 24 weeks ]
    Incidence of hypoglycaemia events

  5. Incidence of adverse events(AEs)and Severe adverse events(SAEs) [ Time Frame: up to 24 weeks ]
    Incidence of adverse events(AEs)and Severe adverse events(SAEs)



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT02303730


Locations
Layout table for location information
China, Shanghai
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
Shanghai, Shanghai, China, 200032
Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital
Shanghai, Shanghai, China
Department of Endocrinology and Metabolism,Huadong Hospital
Shanghai, Shanghai, China
Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital
Shanghai, Shanghai, China
Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital
Shanghai, Shanghai, China
Sponsors and Collaborators
Fudan University
Huadong Hospital
Shanghai Minhang Central Hospital
Shanghai 6th People's Hospital
Shanghai Changzheng Hospital
Investigators
Layout table for investigator information
Principal Investigator: Xin Gao, doctor Fudan University
Publications:

Layout table for additonal information
Responsible Party: Xin Gao, vice-president, Fudan University
ClinicalTrials.gov Identifier: NCT02303730    
Other Study ID Numbers: ESR-14-10096
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Xin Gao, Fudan University:
Diabetes
Non-alcoholic Fatty Liver Disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Insulin Glargine
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists