Effect of Exenatide on Liver and Heart Fat and Inflammation

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01951651
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Exenatide; Drug: Glipizide	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Exenatide Treatment on Myocardial Fat Content, Left Ventricular Function, and Vascular Inflammation in Patients With Type 2 Diabetes Mellitus
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Exenatide 10 micrograms injected subcutaneously twice daily for 6 months	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.; Other Names: Byetta
Experimental: Glipizide Glipizide 5 mg (tablet), one tablet twice daily orally for 6 months	Drug: 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.; Other Names: Glucotrol

Outcome Measures

Primary Outcome Measures

1. Myocardial Fat Content [6 months]

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

2. Hepatic Fat Content [6 months]

   Hepatic fat content following intervention in patients with type 2 diabetes

Secondary Outcome Measures

1. Left Ventricular Ejection Fraction (LVEF)(%). [6 months]

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

2. Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%) [6 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor College of Medicine

Investigators

• Principal Investigator: Mandeep Bajaj, MD, Baylor College of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mandeep Bajaj, Professor of Medicine, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT01951651
• Other Study ID Numbers: H-26030
• First Posted: Sep 26, 2013
• Last Update Posted: May 16, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Mandeep Bajaj, Professor of Medicine, Baylor College of Medicine: Diabetes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation; Exenatide; Glipizide

Study Results

Participant Flow

Arm/Group Title	Exenatide	Glipizide
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.
Period Title: Overall Study
STARTED	12	12
COMPLETED	8	10
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Exenatide	Glipizide	Total
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.	Total of all reporting groups
Overall Participants	8	10	18
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	10 100%	18 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 25%	4 40%	6 33.3%
Male	6 75%	6 60%	12 66.7%
Region of Enrollment (participants) [Number]
United States	8 100%	10 100%	18 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

One patient assigned to the glipizide treatment arm did not complete the myocardial fat content study (MRS) following 6 months of treatment

Arm/Group Title	Exenatide	Glipizide
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.
Measure Participants	8	9
Mean (Standard Error) [percentage of myocardium content]	1.7 (0.4)	1.1 (0.2)

2. Primary Outcome

Title	Hepatic Fat Content
Description	Hepatic fat content following intervention in patients with type 2 diabetes
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

One patient assigned to the glipizide treatment arm did not complete the hepatic fat content study (MRS) following 6 months of treatment

Arm/Group Title	Exenatide	Glipizide
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.
Measure Participants	8	9
Mean (Standard Error) [percent of hepatic fat]	10.9 (1.8)	13.1 (3.5)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

One patient assigned to the glipizide treatment arm did not complete the Left Ventricular Ejection Fraction study (magnetic resonance imaging) following 6 months of treatment

Arm/Group Title	Exenatide	Glipizide
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.
Measure Participants	8	9
Mean (Standard Error) [percent of Left ventricular function]	60 (5)	56 (2)

4. Secondary Outcome

Title	Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)
Description	The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Glipizide
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.
Measure Participants	8	10
Mean (Standard Error) [percentage change from baseline]	-65.0 (8.0)	0.0 (3.0)

Adverse Events

Arm/Group Title	Exenatide		Glipizide
Arm/Group Description	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months 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 5 mg (tablet), one tablet twice daily orally for 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.
All Cause Mortality
	Exenatide		Glipizide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exenatide		Glipizide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide		Glipizide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.