Clinical trial NCT01607450
Conditions: Type 2 Diabetes Mellitus Healthy
Keywords: Type 2 diabetes mellitus lean healthy control
Sponsor: Indiana University
Start date: 2010-05-01; Completion date: 2012-12-01
Enrollment: 33 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:

Arms: arm 1: 12 hour saline (control) infusion prior to PET study arm 2: GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study arm 3: GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study arm 4: GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Interventions: intervention 1: GLP-1 Low Dose intervention 2: GLP-1 Mid-Range Dose intervention 3: GLP-1 High Dose intervention 4: Saline
Intervention descriptions: intervention 1: 0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study intervention 2: 1.5mmol/kg/min for 12 hours prior to PET study intervention 3: 4.0mmol/kg/min GLP-1 for 12 hours prior to PET study intervention 4: Normal saline placebo infusion for 12 hours prior to PET study

Protocol documents: