Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion

Aging Clinical Trial

Official title:

Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04181606
• Other study ID #: 10736
• Status: Completed
• Phase: Early Phase 1
• Start date: February 2, 2022
• Est. completion date: April 12, 2023

Study information

• Verified date: February 2024
• Source: Penn State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will test the central hypothesis that postmenopausal women will demonstrate increased oxygen extraction in active leg muscle during leg cycling exercise while receiving an infusion of Esmolol, a fast-acting β1 selective antagonist, when compared to premenopausal women

Description:

This study will test the central hypothesis that postmenopausal women will demonstrate increased oxygen extraction in active leg muscle during leg cycling exercise while receiving an infusion of Esmolol, a fast-acting β1 selective antagonist, when compared to premenopausal women. β1 selective antagonists (or "β1 blockers") are used to lower heart rate and improve O2 supply-to-demand balance in patients with coronary artery disease. By using esmolol to attenuate the central sympathetic response to exercise (increased heart rate and cardiac output) we can examine peripheral mechanisms of O2 delivery. The current project will evaluate how older postmenopausal women adjust active muscle O2 supply to an acute reduction in systemic O2 delivery during large muscle dynamic exercise when compared to younger premenopausal women.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: April 12, 2023
• Est. primary completion date: April 12, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

3.1 Inclusion Criteria

1. Capable of giving informed consent

2. Premenopausal women ages 18-35 years OR post-menopausal women ages 55-70 years

3. Satisfactory medical history and physical exam, as determined by a CRC clinician

4. Not currently taking medications affecting heart rate or contractility

5. Fluent in written and spoken English

3.2 Exclusion Criteria

Participants who will not be studied are those who:

1. Are less than 19 years of age or more than 70 years of age

2. Are pregnant or lactating

3. Are prisoners or institutionalized individuals or unable to consent

4. Diagnosed renal failure (Creatinine >2.0 mg/dl)

5. Diagnosed liver disease (ALT and AST 2 times normal)

6. Diagnosed Reynaud's disease

7. Have uncontrolled diabetes

8. Have uncontrolled hypertension

9. Have a left ventricular ejection fraction < 40%

10. Have a recent history of unstable angina or myocardial infarction (<6 months), unstable angina, or use of nitrate medications within past 2 weeks

10. Severe lung disease (i.e., on supplemental oxygen or frequently use rescue inhalers)

11. Diagnosed bleeding or clotting disorder or recent blood transfusion 12. Have asthma, history of thyroid issues or hyperkalemia 13. Known use of recreational drugs 14. Methylphenidate use

Related Conditions & MeSH terms

• Aging

Intervention

Drug:
• 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).
• Saline infusion
Saline will be rate/volume matched to the calculated esmolol dose.

Other:
• 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.

Locations

Country	Name	City	State
United States	Noll Laboratory	University Park	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
David N. Proctor, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tissue Saturation Index - Active leg muscle	The primary outcome variable is the difference in the change in skeletal muscle oxygenation (TSI%) in the active leg muscle from baseline during recumbent cycling exercise between saline and esmolol (??TSI%) using near-infrared spectroscopy.	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Secondary	Tissue Saturation Index - Inactive forearm muscle	Difference in the change in skeletal muscle oxygenation (TSI%) in the inactive forearm muscle from baseline during recumbent cycling exercise between saline and esmolol (??TSI%) using near-infrared spectroscopy.	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Secondary	Blood Pressure	Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)	At rest and 3 minutes into moderate exercise and heavy exercise.
Secondary	Heart Rate	Heart rate recorded via EKG	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Secondary	Cardiac Output	Cardiac Output recorded using bioimpedance cardiography	Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.