Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R21HL092799 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Saline | Other | 12 hour saline (control) infusion prior to PET study |
|
| GLP-1 Low dose | Experimental | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
|
| GLP-1 Mid-Range Dose | Experimental | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
|
| GLP-1 High Dose | Experimental | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-1 Low Dose | Drug | 0.5mmol/kg/hr GLP-1 for 12 hours prior to PET study |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Glucose Uptake. | Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0. | After 12 hours of glucagon-like peptide 1 (GLP-1) exposure |
| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Blood Flow | Myocardial perfusion derived from acetate kinetics | After 12 hours of GLP-1 exposure |
| Myocardial Total Oxidation Rate | MVO2 derived from acetate kinetics |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kieren J Mather, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana Clinical Research Center | Indianapolis | Indiana | 46202 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Lean Placebo | 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study |
| FG001 | Lean GLP-1 Mid-Range Dose | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| FG002 | Type 2 DM GLP-1 Mid-Range Dose | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| FG003 | Lean GLP-1 Low Dose | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
| FG004 | Type 2 DM GLP-1 Low Dose | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
| FG005 | Lean GLP-1 High Dose | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study |
| FG006 | Type 2 DM GLP-1 High Dose | GLP-1 High Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lean Saline | 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study |
| BG001 | Lean GLP-1 0.5 Pmol/kg/Min | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Myocardial Glucose Uptake. | Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0. | Posted | Mean | Standard Deviation | umol/min/100g | After 12 hours of glucagon-like peptide 1 (GLP-1) exposure |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lean Saline | 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | General disorders | Systematic Assessment | Nausea associated with the infusion of GLP-1 |
This was a dose-finding study of myocardial responses to systemically infused GLP-1. After ascertaining no detectable response in controls with low dose, we completed mid dose studies. Finding an important difference there we did not do the high dose
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kieren J Mather MD FRCPC | Indiana University | 317-278-7826 | kmather@iu.edu |
Not provided
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| 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 |
|
|
| After 12 hours of GLP-1 exposure |
| Cardiac Index | Impedance cardiography-derived measurement of cardiac index, assessed following 12 hour exposure to treatment condition concurrent with the PET measurements. | After 12 hours of GLP-1 exposure |
| GLP-1 Concentrations | Achieved GLP-1 concentrations at the end of the 12 hour treatment exposure | After 12 hours of GLP-1 exposure |
| BG002 | Type 2 DM GLP-1 0.5 Pmol/kg/Min | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
| BG003 | Lean GLP-1 1.5 Pmol/kg/Min | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| BG004 | Type 2 DM GLP-1 1.5 Pmol/kg/Min | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| BG005 | Lean GLP-1 4.0 Pmol/kg/Min | GLP-1 High Dose:4.0 pmol/kg/min for 12 hours prior to PET study |
| BG006 | Type 2 DM GLP-1 4.0 Pmol/kg/Min | GLP-1 High Dose:4.0 pmol/kg/min for 12 hours prior to PET study |
| BG007 | Total | Total of all reporting groups |
| years |
|
| Gender | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (kg/m2) | Mean | Standard Deviation | kg/m^2 |
|
| HbA1c (%) | Mean | Standard Deviation | % |
|
GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study |
| OG003 | Lean GLP-1 1.5 Pmol/kg/Min | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| OG004 | Type 2DM GLP-1 1.5 Pmol/kg/Min | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study |
| OG005 | Lean GLP-1 High Dose | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study |
| OG006 | Type 2 DM GLP-1 High Dose | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study |
|
|
| Secondary | Myocardial Blood Flow | Myocardial perfusion derived from acetate kinetics | Posted | Mean | Standard Deviation | ml/min/100g | After 12 hours of GLP-1 exposure |
|
|
|
| Secondary | Myocardial Total Oxidation Rate | MVO2 derived from acetate kinetics | Posted | Mean | Standard Deviation | ml/min/100g | After 12 hours of GLP-1 exposure |
|
|
|
| Secondary | Cardiac Index | Impedance cardiography-derived measurement of cardiac index, assessed following 12 hour exposure to treatment condition concurrent with the PET measurements. | Analyses performed only on the groups with relevant primary outcome data observed | Posted | Mean | Standard Deviation | L/min/m^2 | After 12 hours of GLP-1 exposure |
|
|
|
| Secondary | GLP-1 Concentrations | Achieved GLP-1 concentrations at the end of the 12 hour treatment exposure | Analyses performed only on the groups with relevant primary outcome data observed | Posted | Mean | Standard Deviation | pmol/L | After 12 hours of GLP-1 exposure |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | Lean GLP-1 0.5 Pmol/kg/Min | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study | 0 | 11 | 1 | 11 |
| EG002 | Type 2 DM GLP-1 0.5 Pmol/kg/Min | GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study | 0 | 1 | 0 | 1 |
| EG003 | Lean GLP-1 1.5 Pmol/kg/Min | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study | 0 | 8 | 0 | 8 |
| EG004 | Type 2 DM GLP-1 1.5 Pmol/kg/Min | GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study | 0 | 7 | 0 | 7 |
| EG005 | Lean GLP-1 4.0 Pmol/kg/Min | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study | 0 | 0 | 0 | 0 |
| EG006 | Type 2 DM GLP-1 4.0 Pmol/kg/Min | GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study | 0 | 0 | 0 | 0 |
|
Not provided
Not provided
| D004700 | Endocrine System Diseases |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |