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

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ClinicalTrials.gov Identifier: NCT00353834
Recruitment Status : Completed
First Posted : July 19, 2006
Results First Posted : January 9, 2018
Last Update Posted : January 9, 2018
Sponsor:
Collaborators:
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Information provided by (Responsible Party):
Joslin Diabetes Center

Brief Summary:

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 or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Exenatide Drug: Glargine Insulin Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : August 2006
Actual Primary Completion Date : September 2010
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. The Primary Endpoint Was 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 ]
    Flow mediated dilation (FMD) of the brachial artery was measured at rest and during reactive hyperemia using a high-resolution 10.0 MHz linear array transducer and an HOI Ultramark 9 system. Reactive hyperemia was produced by inflating a pneumatic tourniquet on the forearm distal to the brachial artery to 50 mmHg above the systolic BP for 5 minutes, then deflating it . Brachial artery diameter was measured before inflation of the cuff and 1-2 minutes after cuff deflation and expressed as the percentage change. This protocol is described in detail elsewhere. This was performed fasting, 2, and 4 hours after the meal challenge at baseline and 3 months.


Secondary Outcome Measures :
  1. 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 ]
    Trinitroglycerin (TNG) response evaluates endothelium independent vasodilation. The brachial artery was scanned before and 5 minutes after sublingual administration of 400 ug of trinitroglycerin. This was performed only at 4 hours following the test meal and fifteen minutes after completion of the FMD study to allow for the brachial artery to return to baseline. This was performed at both the baseline and 3 month visits.

  2. 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 ]
  3. 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 ]
  4. 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 ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Joslin Diabetes Center
ClinicalTrials.gov Identifier: NCT00353834     History of Changes
Other Study ID Numbers: CHS #05-45
First Posted: July 19, 2006    Key Record Dates
Results First Posted: January 9, 2018
Last Update Posted: January 9, 2018
Last Verified: December 2017

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
Insulin
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists