The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes - Full Text View

Sponsors and Collaborators:	Joslin Diabetes Center Amylin Pharmaceuticals, Inc. Eli Lilly and Company
Information provided by:	Joslin Diabetes Center
ClinicalTrials.gov Identifier:	NCT00353834

Purpose

The main goals of the study are to evaluate the effect of Exenatide on endothelial-dependent vasodilation, as measured by flow mediated dilation (FMD), to evaluate the effect on endothelial-independent vasodilation, as measured by nitroglycerin (TNG) response, and to evaluate the effect on arterial stiffness, as measured by pulse wave analysis (PWA). We will also measure the effects on various markers of endothelial function, subclinical inflammation, fibrinolysis, and oxidative stress. The control group for the study will receive Lantus insulin, with a goal of similar glycemic control between the treatment and control groups.

Specific Aims

We will test the following hypotheses:

Treatment of patients with type 2 diabetes who are inadequately controlled by monotherapy with a Sulfonylurea (SU) or Metformin, or on combination therapy of a SU and Metformin with Exenatide (GLP-1 mimetic) will result in improved endothelial dependent vasodilation, as measured by FMD, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels.
Treatment with Exenatide (GLP-1 mimetic) will result in improved arterial stiffness, as measured by AI by PWA, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels.
Endothelial dependent vasodilation, as measured by FMD, and arterial stiffness, as measured by AI, measured in the postprandial state (following a standard test meal) will be improved following treatment with Exenatide as compared to treatment with once daily basal insulin (Lantus).
Treatment will result in no improvement in endothelial-independent vasodilation, as measured by a response to TNG, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels.
Treatment with Exenatide, compared with treatment with Lantus, will result in a reduction in various plasma markers of inflammation (CRP, TNFA, IL6), endothelial activation (ICAM, VCAM, endothelin 1), fibrinolysis (PAI-1 protein, PAI-1 activity), and oxidative stress (FOX2).

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Exenatide Drug: Glargine Insulin	Phase IV

MedlinePlus related topics: Diabetes

Drug Information available for: Insulin Exenatide Insulin glargine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	The Effect of Exenatide Compared to Lantus Insulin on Vascular Function Before and After a Meal Tolerance Test in Patients With Type 2 Diabetes

Further study details as provided by Joslin Diabetes Center:

Primary Outcome Measures:

The primary endpoint will be the change in FMD at the end of the study compared to baseline measurements in subjects treated with Exenatide compared to subjects treated with Lantus.

Secondary Outcome Measures:

First will be the changes in TNG stimulated arterial dilation (endothelial-independent) in subjects treated with Exenatide compared with subjects treated with Lantus at the end of the study compared to baseline measurements
Second will be the change in arterial stiffness, as measured by PWA, in subjects treated with Exenatide compared with subjects treated with Lantus at the end of the study compared to baseline measurements.
Third will be the changes in markers of endothelial function, inflammation, fibrinolysis, and oxidative stress in subjects treated with Exenatide compared with subjects treated with Lantus at the end of the study compared to baselin
Fourth will be changes in insulin, glucose, c-peptide, lipids, and FFA responses following the MTT in subjects treated with Exenatide compared with subjects treated with Lantus at the end of the study compared to baseline measurement

Estimated Enrollment:	72
Study Start Date:	July 2006
Estimated Study Completion Date:	December 2007

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age 18-75
Type 2 Diabetes (diagnosed at least 3 months prior to study)
HbA1c: above 7.0 and less than or equal to 10.0
At least one HbA1c over preceding 3-6 months, and HbA1c at screening, with less than 1% difference between lowest and highest values
Stable doses of antidiabetic medications (SU and/or Metformin) for 3 months
reproductive age females must have negative urine HCG at screening, and be using appropriate contraception during the study or be surgically sterile
postmenopausal woman
stable weight for 3 months prior to study (+/- 2kg)
willingness to participate in the study

Exclusion Criteria:

Type 1 diabetes
Type 2 diabetes less than 3 months in duration
HbA1c less than 7.0 or greater than 10
age less than 18 or greater than 75
pregnant or planning to become pregnant during study period
current insulin therapy or insulin within 6 months prior to study
current use of Thiazolidinedione or within 6 months prior to study
current use of Nateglinide or Repaglinide
current use of an Alpha-glucosidase Inhibitor
current weight loss program
active smoker, or quit smoking within preceding 6 months
creatinine greater than 2.0 mg/dL
total cholesterol greater than 300 mg/dL
triglycerides greater than 600 mg/dL
blood pressure greater than 160/105 mmHg
ALT/AST greater than twice the upper limit of normal
any other medical condition that may interfere with trial participation or trial results
if on Statin: Statin therapy for less than 3 months or dose change within preceding 3 months
if on ACE Inhibitor: ACE Inhibitor therapy for less than 3 months or dose change within preceding 3 months
current use of any medication that is known to alter gastric motility

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00353834

Contacts

Contact: Edward S. Horton, MD	617 732-2428	edward.horton@joslin.harvard.edu
Contact: Allison Cohen, MD	617 732 2428	allison.cohen@joslin.harvard.edu

Sponsors and Collaborators

Joslin Diabetes Center

Amylin Pharmaceuticals, Inc.

Eli Lilly and Company

Investigators

Principal Investigator:

Edward S. Horton, MD

Joslin Diabetes Center

More Information

No publications provided

Study ID Numbers:	CHS #05-45
Study First Received:	July 18, 2006
Last Updated:	July 18, 2006
ClinicalTrials.gov Identifier:	NCT00353834 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Joslin Diabetes Center:

endothelial dysfunction
subclinical inflammation
flow mediated brachial artery dilation

pulse wave analysis
glucagon like polypeptide mimetics
type 2 diabetes mellitus

Study placed in the following topic categories:

Metabolic Diseases
Dilatation, Pathologic
Exenatide
Glucagon
Diabetes Mellitus
Endocrine System Diseases
Insulin

Inflammation
Hypoglycemic Agents
Diabetes Mellitus, Type 2
Glargine
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder

Additional relevant MeSH terms:

Hypoglycemic Agents
Metabolic Diseases
Exenatide
Physiological Effects of Drugs
Diabetes Mellitus, Type 2

Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Pharmacologic Actions
Insulin

ClinicalTrials.gov processed this record on May 07, 2009