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

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Exenatide SC
Exenatide IV
Placebo SC
Exendin-9
Placebo IV
Sponsored by
Carl T. Hayden VA Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Type 2 diabetes mellitus, Impaired glucose tolerance

Eligibility Criteria

35 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Phoenix VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Exenatide SC (Sub-study 1)

Exenatide IV (Sub-study 2)

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
August 13, 2010
Last Updated
May 12, 2014
Sponsor
Carl T. Hayden VA Medical Center
Collaborators
American Diabetes Association, Amylin Pharmaceuticals, LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT01181986
Brief Title
The Study of Exenatide Action on Vessel Function in Type 2 Diabetes and Prediabetes
Official Title
Exenatide and Postprandial Endothelial Dysfunction: Effects and Mechanisms
Study Type
Interventional

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Carl T. Hayden VA Medical Center
Collaborators
American Diabetes Association, Amylin Pharmaceuticals, LLC.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Type 2 diabetes mellitus, Impaired glucose tolerance

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exenatide SC (Sub-study 1)
Arm Type
Experimental
Arm Description
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.
Arm Title
Exenatide IV (Sub-study 2)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Exenatide SC
Other Intervention Name(s)
Byetta, exendin-4
Intervention Description
Exenatide 5-10 ug sc BID/10 days
Intervention Type
Drug
Intervention Name(s)
Exenatide IV
Other Intervention Name(s)
exendin-4, Byetta
Intervention Description
50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days
Intervention Type
Drug
Intervention Name(s)
Placebo SC
Other Intervention Name(s)
placebo
Intervention Description
Placebo sc BID/10days
Intervention Type
Drug
Intervention Name(s)
Exendin-9
Other Intervention Name(s)
exendin-(9-39)
Intervention Description
Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.
Intervention Type
Drug
Intervention Name(s)
Placebo IV
Other Intervention Name(s)
placebo
Intervention Description
Intravenous infusion for 45 minutes on 1 out of 3 visits
Primary Outcome Measure Information:
Title
Reactive Hyperemia Index (RHI)
Description
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.
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)
Secondary Outcome Measure Information:
Title
Plasma Triglycerides
Description
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.
Time Frame
0, 2, 4, 6 and 8 hours post-study drug on day 11
Title
Plasma Glucose
Description
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.
Time Frame
0, 2, 4, 6, and 8 hours post-study drug on day 11

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juraj Koska, MD, PhD
Organizational Affiliation
Phoenix VA Healthcare System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Phoenix VA Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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