Modulation of Human Myocardial Metabolism by GLP-1 Dose Response
|ClinicalTrials.gov Identifier: NCT01607450|
Recruitment Status : Completed
First Posted : May 30, 2012
Results First Posted : February 17, 2016
Last Update Posted : February 17, 2016
The objective of this proposal is to provide quantitative dose-response data for effects of GLP-1 on myocardial glucose uptake in healthy control subjects and obese type 2 diabetic subjects, in support of the design of later studies evaluating therapeutic applications of GLP-1 to heart disease.
Aim 1: To measure the effects of GLP-1 infusion on myocardial fuel selection in lean healthy humans under fasting (fatty acid-dominant) conditions. Four groups of 10 lean healthy subjects will be studied during infusions of 0 (saline control), 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 (one study per subject). Cardiac metabolism will be measured using PET, using a dual-tracer approach which allows measurement of myocardial glucose uptake (the primary endpoint) along with total oxidation rate and myocardial perfusion (secondary endpoints). In concert with measures of circulating metabolites and regulatory hormones, the investigators will produce the most comprehensive assessment of actions of GLP-1 on myocardial metabolism in humans to date. Effects of each dose will be compared to the saline control, plus the investigators will combine all data and use nonlinear curve-fitting to derive sensitivity (ED50) and maximal responses for GLP-1 effects on myocardial glucose uptake.
Aim 2: To measure the effects of GLP-1 infusion on myocardial fuel selection in obese type 2 diabetic humans under fasting (fatty acid-dominant) conditions Four groups of 10 obese type 2 diabetic subjects will be studied during infusions of 0, 0.5, 1.5, and 4.0 pmol/kg/min GLP-1 as under Aim 1. Analyses will be parallel to those described under Aim 1. Results from Aims 1 and 2 will be combined to allow direct comparison of the dose-response between nondiabetic control and type 2 diabetic subjects.
No literature has been published to inform dose selection in the design of clinical trials of GLP-1 for modulation of heart fuel selection. With our expertise and experience in PET measurement of heart metabolism in diabetes, the investigators are uniquely positioned to fill this gap in knowledge. These studies are a necessary preamble to further evaluation of the potential for GLP-1 based treatments in heart disease.
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus Healthy||Drug: GLP-1 Low Dose Drug: GLP-1 Mid-Range Dose Drug: GLP-1 High Dose Drug: Saline||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Modulation of Human Myocardial Metabolism by GLP-1 Dose Response|
|Study Start Date :||May 2010|
|Primary Completion Date :||December 2012|
|Study Completion Date :||December 2012|
12 hour saline (control) infusion prior to PET study
Normal saline placebo infusion for 12 hours prior to PET study
Other Name: Normal Saline
Experimental: GLP-1 Low dose
GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study
Drug: GLP-1 Low Dose
0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study
Experimental: GLP-1 Mid-Range Dose
GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study
Drug: GLP-1 Mid-Range Dose
1.5mmol/kg/min for 12 hours prior to PET study
Experimental: GLP-1 High Dose
GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Drug: GLP-1 High Dose
4.0mmol/kg/min GLP-1 for 12 hours prior to PET study
- Myocardial Glucose Uptake. [ Time Frame: After 12 hours of glucagon-like peptide 1 (GLP-1) exposure ]Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0.
- Myocardial Blood Flow [ Time Frame: After 12 hours of GLP-1 exposure ]Myocardial perfusion derived from acetate kinetics
- Myocardial Total Oxidation Rate [ Time Frame: After 12 hours of GLP-1 exposure ]MVO2 derived from acetate kinetics
- Cardiac Index [ Time Frame: After 12 hours of GLP-1 exposure ]Impedance cardiography-derived measurement of cardiac index, assessed following 12 hour exposure to treatment condition concurrent with the PET measurements.
- GLP-1 Concentrations [ Time Frame: After 12 hours of GLP-1 exposure ]Achieved GLP-1 concentrations at the end of the 12 hour treatment exposure
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01607450
|United States, Indiana|
|Indiana Clinical Research Center|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Kieren J Mather, MD||Indiana University|