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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01181986
Recruitment Status : Completed
First Posted : August 16, 2010
Results First Posted : April 28, 2014
Last Update Posted : May 20, 2014
Sponsor:
Collaborators:
American Diabetes Association
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
Juraj Koska, Carl T. Hayden VA Medical Center

Tracking Information
First Submitted Date  ICMJE August 13, 2010
First Posted Date  ICMJE August 16, 2010
Results First Submitted Date  ICMJE December 26, 2013
Results First Posted Date  ICMJE April 28, 2014
Last Update Posted Date May 20, 2014
Study Start Date  ICMJE August 2010
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 13, 2010)
Endothelial function [ Time Frame: Days 1 or 11 of intervention ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2014)
  • 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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Study of Exenatide Action on Vessel Function in Type 2 Diabetes and Prediabetes
Official Title  ICMJE Exenatide and Postprandial Endothelial Dysfunction: Effects and Mechanisms
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • Drug: Exenatide SC
    Exenatide 5-10 ug sc BID/10 days
    Other Name: Byetta, exendin-4
  • 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, Byetta
  • Drug: Placebo SC
    Placebo sc BID/10days
    Other Name: placebo
  • Drug: 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Exenatide SC
    • Drug: Placebo SC
  • 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).
    Interventions:
    • Drug: Exenatide IV
    • Drug: Exendin-9
    • Drug: Placebo IV
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2013)
76
Original Estimated Enrollment  ICMJE
 (submitted: August 13, 2010)
80
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01181986
Other Study ID Numbers  ICMJE 1-10-CT-31
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Juraj Koska, Carl T. Hayden VA Medical Center
Study Sponsor  ICMJE Carl T. Hayden VA Medical Center
Collaborators  ICMJE
  • American Diabetes Association
  • Amylin Pharmaceuticals, LLC.
Investigators  ICMJE
Principal Investigator: Juraj Koska, MD, PhD Phoenix VA Healthcare System
PRS Account Carl T. Hayden VA Medical Center
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP