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

NCT00353834 | Completed Phase 4 Results

• 1 other identifier: CHS #05-45
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 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. 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).

Conditions

Type 2 Diabetes Mellitus

Keywords

endothelial dysfunction; subclinical inflammation; flow mediated brachial artery dilation; pulse wave analysis; glucagon like polypeptide mimetics; type 2 diabetes mellitus

Outcome Measures

Primary Outcomes (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.

  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.

  Baseline and End of Study

Secondary Outcomes (4)

• 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

  Baseline and end of study

• 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.

  Baseline and end of study

• 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

  Baseline and end of study

• 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

  Baseline and end of study

Study Arms (2)

Glargine insulin

ACTIVE COMPARATOR

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

Exenatide

EXPERIMENTAL

Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks.

Drug: Exenatide

Interventions

Exenatide DRUG

Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks

Also known as: Byetta

Exenatide

Glargine Insulin DRUG

Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.

Also known as: Lantus insulin

Glargine insulin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• Amylin Pharmaceuticals, LLC.: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Exenatide; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Edward S. Horton, MD
• Organization: Joslin Diabetes Center

edward.horton@joslin.harvard.edu

6173091995

Study Officials

• Edward S. Horton, MD

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2006
• First Posted: July 19, 2006
• Study Start: August 1, 2006
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: January 9, 2018
• Results First Posted: January 9, 2018

Record last verified: 2017-12

Locations

US (1)