The Study of Exenatide Action on Vessel Function in Type 2 Diabetes and Prediabetes

NCT ID: NCT01181986

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2012-12-31

Brief Summary

The purpose of this investigation is to evaluate whether exenatide, a type 2 diabetes medication, will improve the function of the innermost part of the arterial wall called the endothelium after a fat-enriched meal and to determine how this occurs. The results of this study will help to determine and understand a novel action of this group of diabetes medications based on the action of naturally occuring gut substances called incretins. This may have a significant impact on cardiovascular health in patients with early and longstanding diabetes.

Detailed Description

Two independent, double-blinded, crossover substudies will be conducted to test the effect of exenatide on daylong post-meal and fasting endothelial function. We will measure endothelial function measured by peripheral arterial tonometry (EndoPAT2000, Itamar Inc.). Patients with recent onset (<3 years) or established (>5 years, Substudy 1 only) diabetes and impaired sugar tolerance (Substudy 2 only) will be studied. The plan is to complete studies in 75 patients (40 in Substudy 1 and 35 in Substudy 2).

In Substudy 1 patients will get twice a day a skin injection of exenatide (Byetta) or identically looking placebo for 10 days, separated by 14-day period. On the next day after each treatemnt period (day 11), they get just one injection and eat a fat-enriched breakfast. A fatty lunch of similar caloric content will be given 4 hours following the breakfast. Endothelial function will be measured just prior to the injection and every 2 hours for total 8 hours.

In Substudy 2, patients on 3 different days will get infusion of exenatide withg or without a blocking drug exendin-9, and a control test with placebo without exendin-9. Endothelial function will be measured before the infusion and 2 hours later during the final 15 minutes of the infusion cocktails. Patients will not eat any meal during the test visits.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Exenatide SC (Sub-study 1)

Study groups will be individuals with recent onset (\<3 years) or established (\>5 years) T2D. The plan is to achieve 40 complete studies of subcutaneous injection of exenatide BID (Byetta®, 5 or 10 µg) or identically looking Placebo SC for 10 days, separated by 14-day washout period. On the next day after each treatment phase, a single dose of the assigned medication will be injected just before a fat-enriched breakfast meal. A lunch meal of similar caloric and nutrient content will be administered 4 hours following the breakfast meal. Endothelial function will be measured just prior to the injection and every 2 hours during 8-hour post-breakfast period.

Group Type: EXPERIMENTAL

Exenatide SC

Intervention Type: DRUG

Exenatide 5-10 ug sc BID/10 days

Placebo SC

Intervention Type: DRUG

Placebo sc BID/10days

Exenatide IV (Sub-study 2)

Study group will be individuals with recent onset (\<1 year) T2D on diet and impaired glucose tolerance. The plan is to achieve 35 complete studies. The intervention will include 3 randomly ordered visits with intravenous infusion of exenatide in the presence (v1) or absence (v2) of GLP-1 receptor inhibitor exendin-9, and a control test with Placebo IV without exendin-9 (v3). Endothelial function will be measured at baseline and 2 hours later during the final 15 minutes of the infusion cocktails. Study participants will remain fasting during the test visit (3 hours total).

Group Type: EXPERIMENTAL

Exenatide IV

Intervention Type: DRUG

50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days

Exendin-9

Intervention Type: DRUG

Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.

Placebo IV

Intervention Type: DRUG

Intravenous infusion for 45 minutes on 1 out of 3 visits

Interventions

Exenatide SC

Exenatide 5-10 ug sc BID/10 days

Intervention Type: DRUG

Exenatide IV

50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days

Intervention Type: DRUG

Placebo SC

Placebo sc BID/10days

Intervention Type: DRUG

Exendin-9

Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.

Intervention Type: DRUG

Placebo IV

Intravenous infusion for 45 minutes on 1 out of 3 visits

Intervention Type: DRUG

Other Intervention Names

Byetta, exendin-4; exendin-4, Byetta; placebo; exendin-(9-39); placebo

Eligibility Criteria

Inclusion Criteria

• US Veterans
• type 2 diabetes mellitus (T2D) diagnosed within 3 years with good glycemic control on diet, metformin, or sulfonylurea agents or combinations of these agents (HbA1c ≤8.0%)
• T2D diagnosed ≥ 5 years prior to study enrollment
• Impaired glucose tolerance

Exclusion Criteria

• T2D not meeting inclusion above criteria for duration of diabetes or HbA1c values
• known or suspected T1D (early onset age, low body mass index, lack of family history)
• TZD use in the prior 3 months
• prior regular use of insulin
• Creatinine >2.0 mg/dl or other laboratory or clinical evidence of kidney disease
• anemia
• known active liver disease or hepatic enzyme elevation two-and-a half times above normal
• acute bacterial or viral illness or evidence of other active infection in the past 4 weeks
• stable or unstable angina or other major illness in the past 6 months
• Raynaud's disease or any rheumatic disease affecting fingers
• current regular use of anti-inflammatory medications or antioxidants, including over the counter medications and high dose salicylates (>1 g/day);
• subjects receiving lipid lowering or anti-hypertension medications must be on stable doses for at least 2 months prior to participation.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Diabetes Association

OTHER

Sponsor Role: collaborator

Amylin Pharmaceuticals, LLC.

INDUSTRY

Sponsor Role: collaborator

Carl T. Hayden VA Medical Center

FED

Sponsor Role: lead

Responsible Party

Juraj Koska

Research Health Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juraj Koska, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Phoenix VA Healthcare System

Locations

Phoenix VA Medical Center

Phoenix, Arizona, United States

Countries

United States

Other Identifiers

1-10-CT-31

Identifier Type: -

Identifier Source: org_study_id