The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborators:
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Information provided by (Responsible Party):
Edward Horton, Joslin Diabetes Center
ClinicalTrials.gov Identifier:
NCT00353834
First received: July 18, 2006
Last updated: March 28, 2014
Last verified: March 2014
  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:

  1. 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.
  2. 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.
  3. 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).
  4. 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.
  5. 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 4

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

Resource links provided by NLM:


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. [ Time Frame: Baseline and End of Study ] [ Designated as safety issue: No ]

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 [ Time Frame: Baseline and end of study ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Baseline and end of study ] [ Designated as safety issue: No ]
  • 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 baseline [ Time Frame: Baseline and end of study ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline and end of study ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: August 2006
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Glargine insulin
Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia.
Drug: Glargine Insulin
Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.
Other Name: Lantus insulin
Experimental: Exenatide
Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks.
Drug: Exenatide
Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks
Other Name: Byetta

  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
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, see Learn About Clinical Studies.

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

Locations
United States, Massachusetts
Joslin Diabetes Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Joslin Diabetes Center
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Investigators
Principal Investigator: Edward S. Horton, MD Joslin Diabetes Center
  More Information

No publications provided

Responsible Party: Edward Horton, Senior Investigator, Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT00353834     History of Changes
Other Study ID Numbers: CHS #05-45
Study First Received: July 18, 2006
Last Updated: March 28, 2014
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

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Exenatide
Glargine
Insulin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 31, 2014