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CompletedNCT01181986Updated May 20, 2014Results posted

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

A Phase 4 interventional study of Exenatide SC and Exenatide IV in Type 2 Diabetes Mellitus, sponsored by Carl T. Hayden VA Medical Center. Completed at 1 site in United States. Open to participants aged 35 Years to 70 Years. Per ClinicalTrials.gov, last updated 2014-05-20.

Sponsored by Carl T. Hayden VA Medical Center · Phase 4, Interventional, and Basic science

Phase
Phase 4
Study type
Interventional
Enrollment
76
Allocation
Randomized
Ages
35 Years to 70 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Type 2 Diabetes Mellitus

Keywords

  • Type 2 diabetes mellitus, Impaired glucose tolerance
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,318 are open to participants now.

This study's enrollment of 76 is close to the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

Carl T. Hayden VA Medical Center is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
35 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 4
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
76 participants (actual)

Study arms

  • 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 · 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).

    Drug: Exenatide IV · Drug: Exendin-9 · Drug: Placebo IV

Interventions

  • DrugExenatide SC

    Exenatide 5-10 ug sc BID/10 days

    Also known as: Byetta, exendin-4

  • DrugExenatide IV

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

    Also known as: exendin-4, Byetta

  • DrugPlacebo SC

    Placebo sc BID/10days

    Also known as: placebo

  • DrugExendin-9

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

    Also known as: exendin-(9-39)

  • DrugPlacebo IV

    Intravenous infusion for 45 minutes on 1 out of 3 visits

    Also known as: placebo

06

What researchers measure

Primary outcomes

  1. 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.

    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 outcomes

  1. 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.

    Time frame: 0, 2, 4, 6 and 8 hours post-study drug on day 11

  2. 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.

    Time frame: 0, 2, 4, 6, and 8 hours post-study drug on day 11

07

Results

Posted Apr 28, 2014

Participant flow

Phase 1
Participant flow — Phase 1
MilestoneExenatide Then Placebo (Sub-study 1)Placebo Then Exenatide (Sub-study 1)Exenatide IV (Sub-study 2)
Started192334
Saline+exenatide0032
Saline+placebo0033
Exendin-9+exenatide0033
Completed182232
Not completed112
Withdrew: Lost to follow-up011
Withdrew: Adverse event001
Withdrew: Protocol violation100
Phase 2
Participant flow — Phase 2
MilestoneExenatide Then Placebo (Sub-study 1)Placebo Then Exenatide (Sub-study 1)Exenatide IV (Sub-study 2)
Started18220
Completed18180
Not completed040
Withdrew: Adverse event030
Withdrew: Medical condition010

Outcome measures

PrimaryReactive 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.

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)
Reported as:
Least squares mean · ratio
Reactive Hyperemia Index (RHI)
ratioExenatide (Subs-study 1)Placebo (Sub-study 1)Saline+Exenatide (Sub-study 2)Saline+Placebo (Sub-study 2)Exendin-9+Exenatide (Sub-study 2)
Reactive Hyperemia Index (RHI)1.90 ± 0.0051.79 ± 0.052.24 ± 0.071.95 ± 0.071.99 ± 0.07
Statistical analysis
  • Exenatide (Subs-study 1) vs Placebo (Sub-study 1) · ANCOVA · p = <0.0001Adjusted for treatment sequence, group (diabetes duration) and time.
  • Saline+Exenatide (Sub-study 2) vs Saline+Placebo (Sub-study 2) · ANCOVA · p = 0.006Adjusted for treatment sequence.
  • Saline+Exenatide (Sub-study 2) vs Exendin-9+Exenatide (Sub-study 2) · ANCOVA · p = 0.003Adjusted for treatment sequence.
SecondaryPlasma 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.

Time frame:
0, 2, 4, 6 and 8 hours post-study drug on day 11
Reported as:
Least squares mean · mg/dl
Plasma Triglycerides
mg/dlExenatide (Sub-study 1)Placebo (Sub-study 1)
Plasma Triglycerides175 ± 14230 ± 14
Statistical analysis
  • Exenatide (Sub-study 1) vs Placebo (Sub-study 1) · ANCOVA · p = <0.0001Adjusted for treatment sequence and diabetes duration group.
SecondaryPlasma 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.

Time frame:
0, 2, 4, 6, and 8 hours post-study drug on day 11
Reported as:
Least squares mean · mg/dl
Plasma Glucose
mg/dlExenatide (Sub-study 1)Placebo (Sub-study 1)
Plasma Glucose115 ± 5136 ± 5
Statistical analysis
  • Exenatide (Sub-study 1) vs Placebo (Sub-study 1) · ANCOVA · p = <0.0001

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Exenatide SC (Sub-study 1)—0/41 (0%)16/41 (39%)
Placebo SC (Sub-study 1)—0/41 (0%)3/41 (7.3%)
Saline+Exenatide IV (Sub-study 2)—0/32 (0%)0/32 (0%)
Saline+Placebo (Sub-study 2)—1/33 (3%)0/33 (0%)
Exendin-9+Exenatide IV (Sub-study 2)—0/33 (0%)0/33 (0%)
Most frequent serious events
Most frequent serious events
EventExenatide SC (Sub-study 1)Placebo SC (Sub-study 1)Saline+Exenatide IV (Sub-study 2)Saline+Placebo (Sub-study 2)Exendin-9+Exenatide IV (Sub-study 2)
Acute myocardial infarctionCardiac disorders0/410/340/321/330/33
Most frequent other events
Most frequent other events
EventExenatide SC (Sub-study 1)Placebo SC (Sub-study 1)Saline+Exenatide IV (Sub-study 2)Saline+Placebo (Sub-study 2)Exendin-9+Exenatide IV (Sub-study 2)
NauseaGastrointestinal disorders14/412/410/320/330/33
HeadacheGeneral disorders1/411/410/320/330/33
DiarrheaGastrointestinal disorders1/410/410/320/330/33

Baseline characteristics

Age, Continuous
Age, Continuous(years)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Mean62 ± 660 ± 661 ± 6
Sex: Female, Male
Sex: Female, Male(Participants)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Female022
Male423274
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American6511
White362965
More than one race000
Unknown or Not Reported000
Body mass index
Body mass index(kg/m^2)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Mean33 ± 633 ± 1233 ± 9
Glycated hemoglobin
Glycated hemoglobin(%)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Mean6.6 ± 0.96.1 ± 0.56.4 ± 0.8
Diabetes duration (years)
Diabetes duration (years)(years)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Median6 (1 to 9)0 (0 to 1)6 (1 to 9)
Systolic BP
Systolic BP(mmHg)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Mean128 ± 8125 ± 12127 ± 14
Diastolic BP (mmHg)
Diastolic BP (mmHg)(mmHg)Sub-study 1: Exenatide SCSub-study 2: Exenatide IVTotal
Mean78 ± 880 ± 879 ± 8

2 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Phoenix VA Medical Center
    Phoenix, Arizona 85012, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 20, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01181986
Lead sponsor
Carl T. Hayden VA Medical Center
Collaborators
American Diabetes Association, Amylin Pharmaceuticals, LLC.
Responsible party
Juraj Koska (Research Health Scientist, Carl T. Hayden VA Medical Center) — Principal investigator
First posted
Aug 16, 2010
Start date
Aug 2010
Primary completion
Dec 2012
Completion
Dec 2012
Results posted
Apr 28, 2014
Last update
May 20, 2014

Study contacts

Juraj Koska, MD, PhD
principal investigator · Phoenix VA Healthcare System

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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