The Study of Exenatide Action on Vessel Function in Type 2 Diabetes and Prediabetes
|Type 2 Diabetes Mellitus||Drug: Exenatide SC Drug: Exenatide IV Drug: Placebo SC Drug: Exendin-9 Drug: Placebo IV||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Exenatide and Postprandial Endothelial Dysfunction: Effects and Mechanisms|
- Reactive Hyperemia Index (RHI) [ Time Frame: 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) ]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.
- Plasma Triglycerides [ Time Frame: 0, 2, 4, 6 and 8 hours post-study drug on day 11 ]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.
- Plasma Glucose [ Time Frame: 0, 2, 4, 6, and 8 hours post-study drug on day 11 ]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.
|Study Start Date:||August 2010|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: 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.
Drug: Exenatide SC
Exenatide 5-10 ug sc BID/10 days
Other Name: Byetta, exendin-4Drug: Placebo SC
Placebo sc BID/10days
Other Name: placebo
Experimental: 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).
Drug: Exenatide IV
50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days
Other Name: exendin-4, ByettaDrug: Exendin-9
Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.
Other Name: exendin-(9-39)Drug: Placebo IV
Intravenous infusion for 45 minutes on 1 out of 3 visits
Other Name: placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01181986
|United States, Arizona|
|Phoenix VA Medical Center|
|Phoenix, Arizona, United States, 85012|
|Principal Investigator:||Juraj Koska, MD, PhD||Phoenix VA Healthcare System|