Trial Outcomes & Findings for Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion (NCT NCT04181606)
NCT ID: NCT04181606
Last Updated: 2025-05-13
Results Overview
The primary outcome variable is the change in skeletal muscle oxygenation (∆TSI%) in the active leg muscle from baseline during recumbent cycling using near-infrared spectroscopy. TSI% represent the percentage of oxygenated hemoglobin relative to total hemoglobin in the tissue beneath the NIRS probe. Lower values represent a greater reduction in tissue oxygenation from baseline (greater oxygen extraction and/or reduced oxygen delivery). TSI% = oxy\[heme\] / total\[heme\] x 100
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Results posted on
2025-05-13
Participant Flow
37 Participants were screened for eligibility between February 2, 2022 and April 25, 2023 at the Clinical Research Center in University Park, Pennsylvania (PA). Of these, 30 were considered enrolled.
30 participants were considered enrolled and 27 participants were randomized. The 3 participants who were not randomized dropped out of the study prior to the infusion visit.
Participant milestones
| Measure |
Esmolol, Then Saline
Participants first received esmolol hydrochloride via intravenous infusion.
Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
After a washout period of 45 mins, they then received saline via intravenous infusion (volume/rate matched to the calculated dose of esmolol).
|
Saline, Then Esmolol
Participants first received saline via intravenous infusion (volume/rate matched to the calculated dose of esmolol).
After a washout period of 45 mins, they then received esmolol hydrochloride via intravenous infusion.
Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
|
|---|---|---|
|
First Intervention (up to 1 Hour)
STARTED
|
13
|
14
|
|
First Intervention (up to 1 Hour)
COMPLETED
|
13
|
14
|
|
First Intervention (up to 1 Hour)
NOT COMPLETED
|
0
|
0
|
|
Washout (45 Mins)
STARTED
|
13
|
14
|
|
Washout (45 Mins)
COMPLETED
|
13
|
14
|
|
Washout (45 Mins)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (up to 1 Hour)
STARTED
|
13
|
14
|
|
Second Intervention (up to 1 Hour)
COMPLETED
|
13
|
14
|
|
Second Intervention (up to 1 Hour)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion
Baseline characteristics by cohort
| Measure |
Esmolol, Then Saline
n=13 Participants
Participants first received esmolol hydrochloride via intravenous infusion.
Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
After a washout period of 45 mins, they then received saline via intravenous infusion (volume/rate matched to the calculated dose of esmolol).
|
Saline, Then Esmolol
n=14 Participants
Participants first received saline via intravenous infusion (volume/rate matched to the calculated dose of esmolol).
After a washout period of 45 mins, they then received esmolol hydrochloride via intravenous infusion.
Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Age, Continuous
|
45.0 Years
STANDARD_DEVIATION 18.2 • n=5 Participants
|
44.1 Years
STANDARD_DEVIATION 18.2 • n=7 Participants
|
44.6 Years
STANDARD_DEVIATION 18.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.Population: 11 younger and 12 older at two different exercise intensities (Moderate and Heavy)
The primary outcome variable is the change in skeletal muscle oxygenation (∆TSI%) in the active leg muscle from baseline during recumbent cycling using near-infrared spectroscopy. TSI% represent the percentage of oxygenated hemoglobin relative to total hemoglobin in the tissue beneath the NIRS probe. Lower values represent a greater reduction in tissue oxygenation from baseline (greater oxygen extraction and/or reduced oxygen delivery). TSI% = oxy\[heme\] / total\[heme\] x 100
Outcome measures
| Measure |
Esmolol Infusion
n=23 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=24 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Tissue Saturation Index (TSI) - Active Leg Muscle
Younger - Moderate
|
-5.1 % Total Labile Signal
Standard Deviation 3.2
|
-3.1 % Total Labile Signal
Standard Deviation 2.4
|
|
Tissue Saturation Index (TSI) - Active Leg Muscle
Younger - Heavy
|
-8.7 % Total Labile Signal
Standard Deviation 3.5
|
-6.3 % Total Labile Signal
Standard Deviation 3.6
|
|
Tissue Saturation Index (TSI) - Active Leg Muscle
Older - Moderate
|
-1.5 % Total Labile Signal
Standard Deviation 0.9
|
-0.5 % Total Labile Signal
Standard Deviation 1.1
|
|
Tissue Saturation Index (TSI) - Active Leg Muscle
Older - Heavy
|
-4.1 % Total Labile Signal
Standard Deviation 2.7
|
-2.8 % Total Labile Signal
Standard Deviation 3.2
|
SECONDARY outcome
Timeframe: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.Population: 11 younger, 11 older
The change in skeletal muscle oxygenation (∆TSI%) in the inactive forearm from baseline during recumbent cycling using near-infrared spectroscopy. TSI% represent the percentage of oxygenated hemoglobin relative to total hemoglobin in the tissue beneath the NIRS probe. Lower values represent a greater reduction in tissue oxygenation from baseline (greater oxygen extraction and/or reduced oxygen delivery). TSI% = oxy\[heme\] / total\[heme\] x 100
Outcome measures
| Measure |
Esmolol Infusion
n=22 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=22 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Tissue Saturation Index - Inactive Forearm Muscle
Younger - Moderate
|
-3.3 % Total Labile Signal
Standard Deviation 2.5
|
-1.3 % Total Labile Signal
Standard Deviation 1.6
|
|
Tissue Saturation Index - Inactive Forearm Muscle
Younger - Heavy
|
-5.9 % Total Labile Signal
Standard Deviation 4.5
|
-2.3 % Total Labile Signal
Standard Deviation 3.2
|
|
Tissue Saturation Index - Inactive Forearm Muscle
Older - Moderate
|
-0.1 % Total Labile Signal
Standard Deviation 2.3
|
-0.5 % Total Labile Signal
Standard Deviation 1.8
|
|
Tissue Saturation Index - Inactive Forearm Muscle
Older - Heavy
|
-1.5 % Total Labile Signal
Standard Deviation 2.8
|
-0.4 % Total Labile Signal
Standard Deviation 2.5
|
SECONDARY outcome
Timeframe: At rest and 3 minutes into moderate exercise and heavy exercise.Population: 13 younger, 13 older
Systolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Outcome measures
| Measure |
Esmolol Infusion
n=26 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=26 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Systolic Blood Pressure
Younger - Moderate Intensity
|
119 mmHg
Standard Deviation 9
|
137 mmHg
Standard Deviation 14
|
|
Systolic Blood Pressure
Younger - Heavy Intensity
|
134 mmHg
Standard Deviation 8
|
156 mmHg
Standard Deviation 13
|
|
Systolic Blood Pressure
Older - Rest
|
114 mmHg
Standard Deviation 16
|
116 mmHg
Standard Deviation 11
|
|
Systolic Blood Pressure
Older - Moderate Intensity
|
125 mmHg
Standard Deviation 12
|
145 mmHg
Standard Deviation 14
|
|
Systolic Blood Pressure
Old - Heavy Intensity
|
137 mmHg
Standard Deviation 14
|
173 mmHg
Standard Deviation 24
|
|
Systolic Blood Pressure
Younger - Rest
|
105 mmHg
Standard Deviation 9
|
104 mmHg
Standard Deviation 10
|
SECONDARY outcome
Timeframe: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.Population: 13 Younger, 14 Older
Heart rate recorded via EKG
Outcome measures
| Measure |
Esmolol Infusion
n=27 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=27 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Heart Rate
Younger - Rest
|
64.5 Beats/minute
Standard Deviation 8.7
|
70.0 Beats/minute
Standard Deviation 11.1
|
|
Heart Rate
Younger - Moderate Intensity
|
106.3 Beats/minute
Standard Deviation 11.5
|
115.4 Beats/minute
Standard Deviation 16.4
|
|
Heart Rate
Younger - Heavy Intensity
|
123.1 Beats/minute
Standard Deviation 11.8
|
141.2 Beats/minute
Standard Deviation 18.0
|
|
Heart Rate
Older - Rest
|
60.5 Beats/minute
Standard Deviation 7.8
|
67.2 Beats/minute
Standard Deviation 11.7
|
|
Heart Rate
Older - Moderate Intensity
|
89.9 Beats/minute
Standard Deviation 10.4
|
97.6 Beats/minute
Standard Deviation 13.0
|
|
Heart Rate
Older - Heavy Intensity
|
105.5 Beats/minute
Standard Deviation 13.4
|
118.5 Beats/minute
Standard Deviation 20.6
|
SECONDARY outcome
Timeframe: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.Population: 13 younger, 13 older
Cardiac Output recorded using bioimpedance cardiography
Outcome measures
| Measure |
Esmolol Infusion
n=26 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=26 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Cardiac Output
Younger - Moderate Intensity
|
11.3 Liters/minute
Standard Deviation 2.2
|
12.6 Liters/minute
Standard Deviation 1.9
|
|
Cardiac Output
Younger - Rest
|
5.3 Liters/minute
Standard Deviation 0.9
|
5.9 Liters/minute
Standard Deviation 0.7
|
|
Cardiac Output
Younger - Heavy Intensity
|
13.5 Liters/minute
Standard Deviation 2.0
|
15.9 Liters/minute
Standard Deviation 2.5
|
|
Cardiac Output
Older - Rest
|
5.3 Liters/minute
Standard Deviation 0.8
|
5.8 Liters/minute
Standard Deviation 0.6
|
|
Cardiac Output
Older - Moderate Intensity
|
10.1 Liters/minute
Standard Deviation 1.6
|
11.0 Liters/minute
Standard Deviation 1.2
|
|
Cardiac Output
Older - Heavy Intensity
|
12.3 Liters/minute
Standard Deviation 1.7
|
14.1 Liters/minute
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: At rest and 3 minutes into moderate exercise and heavy exercise.Population: 13 younger, 13 older
Diastolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Outcome measures
| Measure |
Esmolol Infusion
n=26 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=26 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Diastolic Blood Pressure
Younger - Rest
|
66 mmHg
Standard Deviation 8
|
63 mmHg
Standard Deviation 6
|
|
Diastolic Blood Pressure
Younger - Moderate Intensity
|
64 mmHg
Standard Deviation 8
|
59 mmHg
Standard Deviation 11
|
|
Diastolic Blood Pressure
Younger - Heavy Intensity
|
64 mmHg
Standard Deviation 8
|
62 mmHg
Standard Deviation 12
|
|
Diastolic Blood Pressure
Older - Rest
|
69 mmHg
Standard Deviation 9
|
69 mmHg
Standard Deviation 8
|
|
Diastolic Blood Pressure
Older - Moderate Intensity
|
68 mmHg
Standard Deviation 6
|
68 mmHg
Standard Deviation 8
|
|
Diastolic Blood Pressure
Old - Heavy Intensity
|
69 mmHg
Standard Deviation 6
|
68 mmHg
Standard Deviation 12
|
SECONDARY outcome
Timeframe: At rest and 3 minutes into moderate exercise and heavy exercise.Population: 13 younger, 13 older
Mean Arterial Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Outcome measures
| Measure |
Esmolol Infusion
n=26 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=26 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Mean Arterial Pressure
Younger - Rest
|
79 mmHg
Standard Deviation 7
|
77 mmHg
Standard Deviation 6
|
|
Mean Arterial Pressure
Younger - Moderate Intensity
|
82 mmHg
Standard Deviation 7
|
85 mmHg
Standard Deviation 10
|
|
Mean Arterial Pressure
Younger - Heavy Intensity
|
87 mmHg
Standard Deviation 7
|
93 mmHg
Standard Deviation 10
|
|
Mean Arterial Pressure
Older - Rest
|
84 mmHg
Standard Deviation 11
|
85 mmHg
Standard Deviation 8
|
|
Mean Arterial Pressure
Older - Moderate Intensity
|
87 mmHg
Standard Deviation 7
|
94 mmHg
Standard Deviation 10
|
|
Mean Arterial Pressure
Old - Heavy Intensity
|
91 mmHg
Standard Deviation 8
|
103 mmHg
Standard Deviation 14
|
SECONDARY outcome
Timeframe: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.Population: 13 younger, 13 older
Stroke Volume recorded using bioimpedance cardiography
Outcome measures
| Measure |
Esmolol Infusion
n=26 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=26 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Stroke Volume
Younger - Rest
|
84 mL/beat
Standard Deviation 15
|
86 mL/beat
Standard Deviation 13
|
|
Stroke Volume
Younger - Moderate Intensity
|
107 mL/beat
Standard Deviation 20
|
110 mL/beat
Standard Deviation 17
|
|
Stroke Volume
Younger - Heavy Intensity
|
110 mL/beat
Standard Deviation 18
|
114 mL/beat
Standard Deviation 19
|
|
Stroke Volume
Older - Rest
|
88 mL/beat
Standard Deviation 16
|
88 mL/beat
Standard Deviation 17
|
|
Stroke Volume
Older - Moderate Intensity
|
113 mL/beat
Standard Deviation 15
|
114 mL/beat
Standard Deviation 14
|
|
Stroke Volume
Older - Heavy Intensity
|
117 mL/beat
Standard Deviation 14
|
119 mL/beat
Standard Deviation 16
|
SECONDARY outcome
Timeframe: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.Population: 13 younger, 13 older
Systemic Vascular Conductance recorded using bioimpedance cardiography
Outcome measures
| Measure |
Esmolol Infusion
n=26 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=26 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
Systemic Vascular Conductance
Younger - Rest
|
70 mL/minute/mmHg
Standard Deviation 13
|
82 mL/minute/mmHg
Standard Deviation 9
|
|
Systemic Vascular Conductance
Younger - Moderate Intensity
|
141 mL/minute/mmHg
Standard Deviation 27
|
154 mL/minute/mmHg
Standard Deviation 32
|
|
Systemic Vascular Conductance
Younger - Heavy Intensity
|
159 mL/minute/mmHg
Standard Deviation 28
|
179 mL/minute/mmHg
Standard Deviation 42
|
|
Systemic Vascular Conductance
Older - Rest
|
67 mL/minute/mmHg
Standard Deviation 8
|
72 mL/minute/mmHg
Standard Deviation 7
|
|
Systemic Vascular Conductance
Older - Moderate Intensity
|
117 mL/minute/mmHg
Standard Deviation 14
|
118 mL/minute/mmHg
Standard Deviation 8
|
|
Systemic Vascular Conductance
Older - Heavy Intensity
|
132 mL/minute/mmHg
Standard Deviation 15
|
136 mL/minute/mmHg
Standard Deviation 14
|
SECONDARY outcome
Timeframe: Last 60 seconds of Moderate and Heavy ExercisePopulation: 9 younger, 12 older
Change in deoxygenated hemoglobin (∆HHb) in the inactive forearm muscle from baseline during recumbent cycling exercise using near-infrared spectroscopy (NIRS) relative to the Total Labile Signal. ∆HHb is an index of oxygen extraction obtained using NIRS. The total labile signal is defined as the difference between the highest observed HHb value during 5 minutes of limb occlusion at 250 mmHg and the lowest observed HHb value observed during reperfusion following removal of the occlusion. Greater ∆HHb values indicate greater oxygen extraction in the tissue under the NIRS probe.
Outcome measures
| Measure |
Esmolol Infusion
n=21 Participants
Drug: Esmolol Hydrochloride Dosage form: Intravenous Infusion Dosage/Frequency: 0.5 mg/(kg Fat Free Mass·min) for 3 min followed by a maintenance infusion of 0.25 mg/(kg Fat Free Mass·min) for remainder of trial, up to a maximum of 1 hour.
Esmolol infusion: The Esmolol loading dose will be 0.5 mg/kg fat free mass/min administered over the first 3 minutes, followed by a maintenance dose of 0.25 mg/kg fat free mass/min for the remainder of the protocol (maximum of 60 minutes).
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
Saline Infusion
n=21 Participants
Saline infusion volume/rate matched to the calculated dose of esmolol.
Saline infusion: Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baseline: Subject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize.
Isometric handgrip exercise: The subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling.
Semi-recumbent cycling: Subjects will pedal for 2-4 minutes at a very light intensity (20W), followed immediately by 5 minutes at a moderate intensity (at a workload intended to elicit 85% of the oxygen consumption observed at the lactate threshold), and 5 minutes of cycling at a heavy intensity (at a workload estimated to elicit oxygen consumption half way between those observed at the lactate threshold and respiratory compensation point). Subjects will then continue cycling at the heavy intensity for 90 seconds while performing isometric handgrip exercise.
|
|---|---|---|
|
∆HHb - Inactive Forearm
Younger - Moderate Exercise
|
8.6 % Total Labile Signal
Standard Deviation 5.7
|
5.0 % Total Labile Signal
Standard Deviation 4.1
|
|
∆HHb - Inactive Forearm
Younger - Heavy Exercise
|
13.5 % Total Labile Signal
Standard Deviation 10.0
|
5.9 % Total Labile Signal
Standard Deviation 7.0
|
|
∆HHb - Inactive Forearm
Older - Moderate Exercise
|
2.9 % Total Labile Signal
Standard Deviation 6.5
|
-3.4 % Total Labile Signal
Standard Deviation 6.1
|
|
∆HHb - Inactive Forearm
Older - Heavy Exercise
|
4.1 % Total Labile Signal
Standard Deviation 9.1
|
-2.6 % Total Labile Signal
Standard Deviation 10.4
|
Adverse Events
Esmolol
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Saline
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place