Trial Outcomes & Findings for Modulation of Human Myocardial Metabolism by GLP-1 Dose Response (NCT NCT01607450)

Results Overview

Myocardial glucose uptake measured using 18FDG PET, quantified using a 3-compartment model with a lumped constant of 1.0.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

33 participants

Primary outcome timeframe

After 12 hours of glucagon-like peptide 1 (GLP-1) exposure

Results posted on

2016-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Lean Placebo 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 Mid-Range Dose GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	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	Lean GLP-1 Low Dose GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 Low Dose GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study
Overall Study STARTED	6	8	7	11	1
Overall Study COMPLETED	6	8	7	11	1
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Modulation of Human Myocardial Metabolism by GLP-1 Dose Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lean Saline n=6 Participants 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 0.5 Pmol/kg/Min n=11 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 0.5 Pmol/kg/Min n=1 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 1.5 Pmol/kg/Min n=7 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 4.0 Pmol/kg/Min GLP-1 High Dose:4.0 pmol/kg/min for 12 hours prior to PET study	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	Total n=33 Participants Total of all reporting groups
Age, Continuous	35.5 years STANDARD_DEVIATION 10.6 • n=5 Participants	38.0 years STANDARD_DEVIATION 6.0 • n=7 Participants	42 years STANDARD_DEVIATION 0 • n=5 Participants	46.0 years STANDARD_DEVIATION 5.8 • n=4 Participants	45.1 years STANDARD_DEVIATION 7.9 • n=21 Participants	—	—	42.7 years STANDARD_DEVIATION 7.9 • n=24 Participants
Gender Female	5 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants	1 participants n=21 Participants	—	—	12 participants n=24 Participants
Gender Male	1 participants n=5 Participants	8 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants	6 participants n=21 Participants	—	—	21 participants n=24 Participants
Region of Enrollment United States	6 participants n=5 Participants	11 participants n=7 Participants	1 participants n=5 Participants	8 participants n=4 Participants	7 participants n=21 Participants	—	—	33 participants n=24 Participants
Body Mass Index (kg/m2)	23.9 kg/m^2 STANDARD_DEVIATION 1.6 • n=5 Participants	23.0 kg/m^2 STANDARD_DEVIATION 1.5 • n=7 Participants	31.0 kg/m^2 STANDARD_DEVIATION 0 • n=5 Participants	22.9 kg/m^2 STANDARD_DEVIATION 1.8 • n=4 Participants	30.3 kg/m^2 STANDARD_DEVIATION 1.7 • n=21 Participants	—	—	25.7 kg/m^2 STANDARD_DEVIATION 1.7 • n=24 Participants
HbA1c (%)	5.47 % STANDARD_DEVIATION 0.40 • n=5 Participants	5.47 % STANDARD_DEVIATION 0.40 • n=7 Participants	7.0 % STANDARD_DEVIATION 0 • n=5 Participants	5.56 % STANDARD_DEVIATION 0.34 • n=4 Participants	8.40 % STANDARD_DEVIATION 3.02 • n=21 Participants	—	—	6.48 % STANDARD_DEVIATION 1.24 • n=24 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Lean Saline n=6 Participants 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 Low Dose n=11 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 Low Dose n=1 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2DM GLP-1 1.5 Pmol/kg/Min n=7 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Myocardial Glucose Uptake.	7.46 umol/min/100g Standard Deviation 8.49	7.22 umol/min/100g Standard Deviation 9.26	0.05 umol/min/100g Standard Deviation 0	20.89 umol/min/100g Standard Deviation 12.47	5.57 umol/min/100g Standard Deviation 19.39	—	—

SECONDARY outcome

Timeframe: After 12 hours of GLP-1 exposure

Myocardial perfusion derived from acetate kinetics

Outcome measures

Outcome measures
Measure	Lean Saline n=6 Participants 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 Low Dose n=11 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 Low Dose n=1 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2DM GLP-1 1.5 Pmol/kg/Min n=7 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Myocardial Blood Flow	34.66 ml/min/100g Standard Deviation 4.60	44.44 ml/min/100g Standard Deviation 9.17	47.61 ml/min/100g Standard Deviation 0	35.30 ml/min/100g Standard Deviation 7.35	51.19 ml/min/100g Standard Deviation 19.39	—	—

SECONDARY outcome

Timeframe: After 12 hours of GLP-1 exposure

MVO2 derived from acetate kinetics

Outcome measures

Outcome measures
Measure	Lean Saline n=6 Participants 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 Low Dose n=11 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 Low Dose n=1 Participants GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2DM GLP-1 1.5 Pmol/kg/Min n=7 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Myocardial Total Oxidation Rate	15.25 ml/min/100g Standard Deviation 2.39	30.21 ml/min/100g Standard Deviation 14.32	65.30 ml/min/100g Standard Deviation 0	18.57 ml/min/100g Standard Deviation 3.78	59.85 ml/min/100g Standard Deviation 30.47	—	—

SECONDARY outcome

Timeframe: After 12 hours of GLP-1 exposure

Population: Analyses performed only on the groups with relevant primary outcome data observed

Impedance cardiography-derived measurement of cardiac index, assessed following 12 hour exposure to treatment condition concurrent with the PET measurements.

Outcome measures

Outcome measures
Measure	Lean Saline n=6 Participants 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 Low Dose GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 Low Dose GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2DM GLP-1 1.5 Pmol/kg/Min n=7 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
Cardiac Index	3.00 L/min/m^2 Standard Deviation 0.52	—	—	2.88 L/min/m^2 Standard Deviation 0.31	2.90 L/min/m^2 Standard Deviation 0.51	—	—

SECONDARY outcome

Timeframe: After 12 hours of GLP-1 exposure

Population: Analyses performed only on the groups with relevant primary outcome data observed

Achieved GLP-1 concentrations at the end of the 12 hour treatment exposure

Outcome measures

Outcome measures
Measure	Lean Saline n=6 Participants 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 Low Dose GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 Low Dose GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2DM GLP-1 1.5 Pmol/kg/Min n=7 Participants GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 High Dose GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study
GLP-1 Concentrations	61.7 pmol/L Standard Deviation 33.5	—	—	302.1 pmol/L Standard Deviation 149.1	307.8 pmol/L Standard Deviation 86.2	—	—

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Lean Saline n=6 participants at risk 12 hour placebo (saline) infusion prior to PET study Placebo: Saline placebo infusion for 12 hours prior to PET study	Lean GLP-1 0.5 Pmol/kg/Min n=11 participants at risk GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 0.5 Pmol/kg/Min n=1 participants at risk GLP-1 Low Dose: 0.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 1.5 Pmol/kg/Min n=8 participants at risk GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Type 2 DM GLP-1 1.5 Pmol/kg/Min n=7 participants at risk GLP-1 Mid-Range Dose: 1.5 pmol/kg/min for 12 hours prior to PET study	Lean GLP-1 4.0 Pmol/kg/Min GLP-1 High Dose: 4.0 pmol/kg/min for 12 hours prior to PET study	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
General disorders Nausea	0.00% 0/6	9.1% 1/11 • Number of events 1	0.00% 0/1	0.00% 0/8	0.00% 0/7	— 0/0	— 0/0

Additional Information

Kieren J Mather MD FRCPC

Indiana University

Phone: 317-278-7826

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place