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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Exenatide and Postprandial Endothelial Dysfunction: Effects and Mechanisms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01181986
• Other study ID #: 1-10-CT-31
• Status: Completed
• Phase: Phase 4
• First received: August 13, 2010
• Last updated: May 12, 2014
• Start date: August 2010
• Est. completion date: December 2012

Study information

• Verified date: May 2014
• Source: Carl T. Hayden VA Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Exenatide SC
Exenatide 5-10 ug sc BID/10 days
• Exenatide IV
50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days
• Placebo SC
Placebo sc BID/10days
• Exendin-9
Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.
• Placebo IV
Intravenous infusion for 45 minutes on 1 out of 3 visits

Locations

Country	Name	City	State
United States	Phoenix VA Medical Center	Phoenix	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Carl T. Hayden VA Medical Center	American Diabetes Association, Amylin Pharmaceuticals, LLC.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reactive Hyperemia Index (RHI)	Greater RHI reflects greater endothelial function. It is calculated as average post-ischemia pulse magnitude divided by average pre-ischemia pulse magnitude. Results are expressed as least-square means of ANCOVA models.	0, 2, 4, 6 and 8 hours on Day 11 (Sub-study 1); 0 and 120 minutes on test Days 1, 2 & 3 (Sub-study 2)	No
Secondary	Plasma Triglycerides	Triglycerides concentrations were measured before and 2, 4, 6 and 8 hours following study drug. Results are expressed as least-square means of ANCOVA models adjusted for sampling time and intervention sequence.	0, 2, 4, 6 and 8 hours post-study drug on day 11	No
Secondary	Plasma Glucose	Plasma glucose was measured before and 2, 4, 6 and 8 hours following study drug administration. Results are expressed as least-square means of ANCOVA models adjusted for sampling time and intervention sequence.	0, 2, 4, 6, and 8 hours post-study drug on day 11	No