Skip to main content
OpenTrials
Completed

NCT Number: NCT01607450

Modulation of Human Myocardial Metabolism by GLP-1 Dose Response

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Healthy Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Indiana Clinical Research Center

Indianapolis, Indiana, 46202, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-60
  • Lean subjects will be defined as having a BMI <25 kg/m2, in good general health, taking no regular medications
  • Diabetic subjects will be obese (BMI >30 kg/m2 but <40 kg/m2), HbA1c 7.0-10.0%, treated with diet and exercise plus oral agents or injected insulin. All diabetic subjects will be treated with injected insulin for 2 weeks prior to study, to avoid potential confounding effects of other antidiabetic agents.

Exclusion criteria

  • Chronic illnesses or infections (other than type 2 diabetes)
  • Known coronary artery disease or abnormal ECG on screening evaluation
  • Blood pressure > 160/100 mmHg on two occasions during screening evaluations. Current use of 3 or fewer blood pressure medications with blood pressure below this cutpoint will be acceptable.
  • Total cholesterol > 240 mg/dL. Current use of 2 or fewer lipid lowering agents with cholesterol below this cutpoint will be acceptable.
  • Diabetic subjects: Treatment with a GLP-1 agonist or DPP4 inhibitor within the past 6 months
  • Known intolerance to injected GLP-1 agonist
  • Treatment with PPAR gamma agonists currently or within the past 6 months
  • Recognized microvascular complications (retinopathy, nephropathy, neuropathy)
  • Unwillingness or inability to use injected insulin for the purposes of this study
  • Chronic pain or other physical conditions which limit ability to remain supine for the duration of the study protocol
  • History of claustrophobia, musculoskeletal or other factors which would result in an inability to comfortably remain within PET scanner gantry for the duration of the imaging protocol
  • Occupational, investigational or other known radiation exposure which, together with the planned radiologic studies, will result in greater than 500 mrem total exposure in a contiguous 12 month period
  • For female participants, current pregnancy

Treatment and study plan

GLP-1 Low Dose

Drug

0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study

GLP-1 Mid-Range Dose

Drug

1.5mmol/kg/min for 12 hours prior to PET study

GLP-1 High Dose

Drug

4.0mmol/kg/min GLP-1 for 12 hours prior to PET study

Saline

Drug

Normal saline placebo infusion for 12 hours prior to PET study

Other names: Normal Saline

Primary outcomes

  1. 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.

Secondary outcomes

  1. Myocardial Blood Flow

    Time frame: After 12 hours of GLP-1 exposure

    Myocardial perfusion derived from acetate kinetics

  2. Myocardial Total Oxidation Rate

    Time frame: After 12 hours of GLP-1 exposure

    MVO2 derived from acetate kinetics

  3. 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.

  4. 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

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
May 30, 2012
Registry last updated
Feb 17, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.