Trial · Interventional

CompletedPhase 4Results postedRegistry data

The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes

NCTNCT00353834Other idCHS #05-45

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Overview

Status: Completed
Phase: Phase 4
Enrollment: 72 participants (actual)
Sponsor: Joslin Diabetes Center · Other
Design: Randomized · Open label (no masking)
Countries: 1 country
United States
Start: Aug 2006
Primary completion: Sept 2010
Completion: Sept 2010
First posted: 19 Jul 2006 (estimated)
Last update posted: 9 Jan 2018
Conditions: Type 2 Diabetes Mellitus

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

200620072008200920102011

Ph 4
The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes
NCT00353834
Aug 2006 to Sept 2010

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The main goals of the study are to evaluate the effect of Exenatide on endothelial-dependent vasodilation, as measured by flow mediated dilation (FMD), to evaluate the effect on endothelial-independent vasodilation, as measured by nitroglycerin (TNG) response, and to evaluate the effect on arterial stiffness, as measured by pulse wave analysis (PWA). We will also measure the effects on various markers of endothelial function, subclinical inflammation, fibrinolysis, and oxidative stress. The control group for the study will receive Lantus insulin, with a goal of similar glycemic control between the treatment and control groups. Specific Aims We will test the following hypotheses: 1. Treatment of patients with type 2 diabetes who are inadequately controlled by monotherapy with a Sulfonylurea (SU) or Metformin, or on combination therapy of a SU and Metformin with Exenatide (GLP-1 mimetic) will result in improved endothelial dependent vasodilation, as measured by FMD, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels. 2. Treatment with Exenatide (GLP-1 mimetic) will result in improved arterial stiffness, as measured by AI by PWA, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels. 3. Endothelial dependent vasodilation, as measured by FMD, and arterial stiffness, as measured by AI, measured in the postprandial state (following a standard test meal) will be improved following treatment with Exenatide as compared to treatment with once daily basal insulin (Lantus). 4. Treatment will result in no improvement in endothelial-independent vasodilation, as measured by a response to TNG, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels. 5. Treatment with Exenatide, compared with treatment with Lantus, will result in a reduction in various plasma markers of inflammation (CRP, TNFA, IL6), endothelial activation (ICAM, VCAM, endothelin 1), fibrinolysis (PAI-1 protein, PAI-1 activity), and oxidative stress (FOX2).

Interventions

ExenatideDrug
Glargine InsulinDrug

Arms2

Active comparator
Glargine insulin
Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia.
Experimental
Exenatide
Exenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks.

Primary outcomes1

Outcomes the sponsor listed as primary.

The Primary Endpoint Was the Change in FMD at the End of the Study Compared to Baseline Measurements in Subjects Treated With Exenatide Compared to Subjects Treated With Lantus.
Time frame · Baseline and End of Study
Registry description
Flow mediated dilation (FMD) of the brachial artery was measured at rest and during reactive hyperemia using a high-resolution 10.0 MHz linear array transducer and an HOI Ultramark 9 system. Reactive hyperemia was produced by inflating a pneumatic tourniquet on the forearm distal to the brachial artery to 50 mmHg above the systolic BP for 5 minutes, then deflating it . Brachial artery diameter was measured before inflation of the cuff and 1-2 minutes after cuff deflation and expressed as the percentage change. This protocol is described in detail elsewhere. This was performed fasting, 2, and 4 hours after the meal challenge at baseline and 3 months.

Secondary outcomes(4)

First Will be the Changes in TNG Stimulated Arterial Dilation (Endothelial-independent) in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurements
Time frame · Baseline and end of study
Registry description
Trinitroglycerin (TNG) response evaluates endothelium independent vasodilation. The brachial artery was scanned before and 5 minutes after sublingual administration of 400 ug of trinitroglycerin. This was performed only at 4 hours following the test meal and fifteen minutes after completion of the FMD study to allow for the brachial artery to return to baseline. This was performed at both the baseline and 3 month visits.
Second Will be the Change in Arterial Stiffness, as Measured by PWA, in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurements.
Time frame · Baseline and end of study
Third Will be the Changes in Markers of Endothelial Function, Inflammation, Fibrinolysis, and Oxidative Stress in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline
Time frame · Baseline and end of study
Fourth Will be Changes in Insulin, Glucose, C-peptide, Lipids, and FFA Responses Following the MTT in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurement
Time frame · Baseline and end of study

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline and End of Study

The Primary Endpoint Was the Change in FMD at the End of the Study Compared to Baseline Measurements in Subjects Treated With Exenatide Compared to Subjects Treated With Lantus.

Group	Value (Percentage dilation)	Spread
Glargine Insulin	5.0	2.3
Exenatide	4.7	2.4

Secondary and other outcome results(4)

Secondary outcomeMean· Baseline and end of study

First Will be the Changes in TNG Stimulated Arterial Dilation (Endothelial-independent) in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurements

Group	Value (Percentage dilation)	Spread
Glargine Insulin	10.7	5.3
Exenatide	11.3	4.5

Secondary outcome· Baseline and end of study

Second Will be the Change in Arterial Stiffness, as Measured by PWA, in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurements.

Group	Value

Secondary outcome· Baseline and end of study

Third Will be the Changes in Markers of Endothelial Function, Inflammation, Fibrinolysis, and Oxidative Stress in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline

Group	Value

Secondary outcome· Baseline and end of study

Fourth Will be Changes in Insulin, Glucose, C-peptide, Lipids, and FFA Responses Following the MTT in Subjects Treated With Exenatide Compared With Subjects Treated With Lantus at the End of the Study Compared to Baseline Measurement

Group	Value

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Glargine InsulinGlargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve fasting blood glucose of 100 mg/dl and avoid hypoglycemia. Glargine Insulin: Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.	0 / 26	0 / 26	0 / 26
ExenatideExenatide 5ug twice daily for 4 weeks followed by 10 ug twice daily for 8 weeks. Exenatide: Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks	0 / 27	0 / 27	0 / 27

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 75 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * age 18-75 * Type 2 Diabetes (diagnosed at least 3 months prior to study) * HbA1c: above 7.0 and less than or equal to 10.0 * At least one HbA1c over preceding 3-6 months, and HbA1c at screening, with less than 1% difference between lowest and highest values * Stable doses of antidiabetic medications (SU and/or Metformin) for 3 months * reproductive age females must have negative urine HCG at screening, and be using appropriate contraception during the study or be surgically sterile * postmenopausal woman * stable weight for 3 months prior to study (+/- 2kg) * willingness to participate in the study Exclusion Criteria: * Type 1 diabetes * Type 2 diabetes less than 3 months in duration * HbA1c less than 7.0 or greater than 10 * age less than 18 or greater than 75 * pregnant or planning to become pregnant during study period * current insulin therapy or insulin within 6 months prior to study * current use of Thiazolidinedione or within 6 months prior to study * current use of Nateglinide or Repaglinide * current use of an Alpha-glucosidase Inhibitor * current weight loss program * active smoker, or quit smoking within preceding 6 months * creatinine greater than 2.0 mg/dL * total cholesterol greater than 300 mg/dL * triglycerides greater than 600 mg/dL * blood pressure greater than 160/105 mmHg * ALT/AST greater than twice the upper limit of normal * any other medical condition that may interfere with trial participation or trial results * if on Statin: Statin therapy for less than 3 months or dose change within preceding 3 months * if on ACE Inhibitor: ACE Inhibitor therapy for less than 3 months or dose change within preceding 3 months * current use of any medication that is known to alter gastric motility

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