Effect of Exenatide on Liver and Heart Fat and Inflammation

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Effect of Exenatide Treatment on Myocardial Fat Content, Left Ventricular Function, and Vascular Inflammation in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951651
• Other study ID #: H-26030
• Status: Completed
• Phase: Phase 4
• First received: September 24, 2013
• Last updated: September 24, 2013
• Start date: April 2010
• Est. completion date: March 2013

Study information

• Verified date: September 2013
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the effect of exenatide on liver and heart (myocardial) fat and inflammation.

Description:

Type 2 diabetics and insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD). The fatty liver is insulin resistant. Individuals with a fatty liver are more likely to have excess intra-abdominal fat as well as a reduction in circulating plasma adiponectin levels. We have previously shown that type 2 diabetes and its associated Non Alcoholic Fatty Liver Disease (NAFLD) is characterized by increased hepatic fat content, decreased circulating adiponectin levels, and hepatic and peripheral (muscle) insulin resistance. Weight loss in humans with Non Alcoholic Fatty Liver Disease is associated with a decrease in hepatic fat content. Exenatide, an incretin based anti-diabetes therapy, enhances glucose-dependent insulin secretion and glucose-dependent suppression of inappropriately high glucagon secretion, improves glycemic control in patients with type 2 diabetes and is associated with weight loss. In rodent studies, exenatide reduces hepatic and myocardial fat and reduces vascular inflammation independent of changes in weight. Exenatide has also been shown to increase plasma adiponectin levels in humans and rodents. Furthermore type 2 diabetics are characterized by an increase in both hepatic and myocardial fat and left ventricular dysfunction, particularly diastolic dysfunction. However, the effect of exenatide therapy on liver and myocardial fat content, as well as left ventricular function in patients with type 2 diabetes has not been previously studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.

2. Patients may be of either sex. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions.

3. Patients must range in age from 30 to 70 years, inclusive.

4. Patients must meet the American Diabetes Association (ADA) criteria (ADA 1997 Criteria: fasting plasma glucose greater than or equal to 126 mg/dl) for the diagnosis of type 2 diabetes mellitus.

5. Patients must be on diet therapy and/or metformin treatment for type 2 diabetes (stable dose)and have a fasting plasma glucose concentration between 126 and 260 mg/dl

6. Patients must have Hematocrit greater than 34 vol%.

7. Subjects whose body weight has been stable over the three months prior to study enrollment will be included.

Exclusion Criteria:

1. Patients must not have type 1 diabetes.

2. Patients must not have a fasting plasma glucose greater than 260 mg/dl.

3. Patients must not have received a thiazolidinedione for at least 3 months prior to randomization.

4. Patients must not be on insulin treatment or have received insulin for more than one week within the previous year prior to entry. Patients should not be on sulfonylureas, sitagliptin, or exenatide treatment.

5. Patients taking systemic glucocorticoids or other medications known to affect glucose tolerance are excluded.

6. Patients taking medications that affect gastrointestinal motility will be excluded.

7. Patients with a history of Congestive Heart Failure, or clinically significant cardiac, liver or kidney disease (creatinine greater than 1.5 mg/dl).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Exenatide
Type 2 diabetic subjects will be randomized to receive either Exenatide 10 micrograms twice daily injected subcutaneously or glipizide 5 mg twice daily orally for 6 months. All subjects will receive baseline measurements of fasting plasma glucose, free fatty acids, plasma adipocytokines, plasma lipids, and glycosylated hemoglobin (HbA1c) as well as measurement of liver and myocardial fat content and left ventricular function with magnetic resonance imaging/spectroscopy. All subjects will also undergo measurements of monocyte inflammatory proteins at baseline. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, adipocytokines, HbA1c, monocyte inflammation, as well as hepatic/myocardial fat content determination and left ventricular function at the end of the 6 months.
• Glipizide
Type 2 diabetic subjects will be randomized to receive either Exenatide 10 micrograms twice daily injected subcutaneously or glipizide 5 mg twice daily orally for 6 months. All subjects will receive baseline measurements of fasting plasma glucose, free fatty acids, plasma adipocytokines, plasma lipids, and glycosylated hemoglobin (HbA1c) as well as measurement of liver and myocardial fat content and left ventricular function with magnetic resonance imaging/spectroscopy. All subjects will also undergo measurements of monocyte inflammatory proteins at baseline. All subjects will undergo repeat measurements of fasting plasma glucose, Free Fatty Acids, adipocytokines, HbA1c, monocyte inflammation, as well as hepatic/myocardial fat content determination and left ventricular function at the end of the 6 months.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial and Hepatic fat content (percentage)	The percentage change in hepatic fat (%) and myocardial fat (%) from baseline as measured by magnetic resonance imaging and spectroscopy (MRS)in patients with type 2 diabetes.	6 months	No
Secondary	left ventricular ejection fraction (LVEF)(%).	The change in Left ventricular function measured as the percentage change in left ventricular ejection fraction (LVEF)(%) from baseline as measured by by magnetic resonance imaging.	6 months	No
Secondary	monocyte inflammatory protein Nuclear Factor kappa-B (NFkappaB) (%)	The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline.	6 months	No