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Effect of Exenatide on Liver and Heart Fat and Inflammation

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Exenatide

Glipizide

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Diabetes

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
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.
Patients must range in age from 30 to 70 years, inclusive.
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.
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
Patients must have Hematocrit greater than 34 vol%.
Subjects whose body weight has been stable over the three months prior to study enrollment will be included.

Exclusion Criteria:

Patients must not have type 1 diabetes.
Patients must not have a fasting plasma glucose greater than 260 mg/dl.
Patients must not have received a thiazolidinedione for at least 3 months prior to randomization.
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.
Patients taking systemic glucocorticoids or other medications known to affect glucose tolerance are excluded.
Patients taking medications that affect gastrointestinal motility will be excluded.
Patients with a history of Congestive Heart Failure, or clinically significant cardiac, liver or kidney disease (creatinine greater than 1.5 mg/dl).

Sites / Locations

Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Exenatide

Glipizide

Arm Description

Exenatide 10 micrograms injected subcutaneously twice daily for 6 months

Glipizide 5 mg (tablet), one tablet twice daily orally for 6 months

Outcomes

Primary Outcome Measures

Myocardial Fat Content

Myocardial fat content following intervention as measured by magnetic resonance imaging and spectroscopy (MRS) in patients with type 2 diabetes.

Hepatic Fat Content

Hepatic fat content following intervention in patients with type 2 diabetes

Secondary Outcome Measures

Left Ventricular Ejection Fraction (LVEF)(%).

Left Ventricular Ejection Fraction following intervention as measured by magnetic resonance imaging in patients with type 2 diabetes.

Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)

The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline.

Full Information

NCT ID

NCT01951651

First Posted

September 24, 2013

Last Updated

April 14, 2016

Sponsor

Baylor College of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01951651

Brief Title

Effect of Exenatide on Liver and Heart Fat and Inflammation

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

April 2010 (undefined)

Primary Completion Date

October 2012 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Baylor College of Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Exenatide

Arm Type

Experimental

Arm Description

Exenatide 10 micrograms injected subcutaneously twice daily for 6 months

Arm Title

Glipizide

Arm Type

Experimental

Arm Description

Glipizide 5 mg (tablet), one tablet twice daily orally for 6 months

Intervention Type

Drug

Intervention Name(s)

Exenatide

Other Intervention Name(s)

Byetta

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Glipizide

Other Intervention Name(s)

Glucotrol

Intervention Description

Primary Outcome Measure Information:

Title

Myocardial Fat Content

Description

Myocardial fat content following intervention as measured by magnetic resonance imaging and spectroscopy (MRS) in patients with type 2 diabetes.

Time Frame

6 months

Title

Hepatic Fat Content

Description

Hepatic fat content following intervention in patients with type 2 diabetes

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Left Ventricular Ejection Fraction (LVEF)(%).

Description

Left Ventricular Ejection Fraction following intervention as measured by magnetic resonance imaging in patients with type 2 diabetes.

Time Frame

6 months

Title

Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)

Description

The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent. 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. Patients must range in age from 30 to 70 years, inclusive. 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. 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 Patients must have Hematocrit greater than 34 vol%. Subjects whose body weight has been stable over the three months prior to study enrollment will be included. Exclusion Criteria: Patients must not have type 1 diabetes. Patients must not have a fasting plasma glucose greater than 260 mg/dl. Patients must not have received a thiazolidinedione for at least 3 months prior to randomization. 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. Patients taking systemic glucocorticoids or other medications known to affect glucose tolerance are excluded. Patients taking medications that affect gastrointestinal motility will be excluded. Patients with a history of Congestive Heart Failure, or clinically significant cardiac, liver or kidney disease (creatinine greater than 1.5 mg/dl).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mandeep Bajaj, MD

Organizational Affiliation

Baylor College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Baylor College of Medicine

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

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Effect of Exenatide on Liver and Heart Fat and Inflammation

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