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

NCT ID: NCT04181606

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-02
• Study Completion Date: 2023-04-25

Brief 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

Detailed 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.

Conditions

Aging

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Esmolol Infusion

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.

Group Type: ACTIVE_COMPARATOR

Esmolol infusion

Intervention Type: DRUG

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

Intervention Type: OTHER

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

Intervention Type: OTHER

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

Intervention Type: OTHER

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

Saline infusion volume/rate matched to the calculated dose of esmolol.

Group Type: PLACEBO_COMPARATOR

Saline infusion

Intervention Type: DRUG

Saline will be rate/volume matched to the calculated esmolol dose.

Pre exercise baseline

Intervention Type: OTHER

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

Intervention Type: OTHER

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

Intervention Type: OTHER

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.

Interventions

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).

Intervention Type: DRUG

Saline infusion

Saline will be rate/volume matched to the calculated esmolol dose.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

Intervention Type: OTHER

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.

Intervention Type: OTHER

Other Intervention Names

Esmolol Hydrochloride; Normal saline solution

Eligibility Criteria

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 Clinical Research Center (CRC) clinician

4. Not currently taking medications affecting heart rate or contractility

5. Fluent in written and spoken English

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 aspartate aminotransferase {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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

David N. Proctor, PhD

OTHER

Sponsor Role: lead

Responsible Party

David N. Proctor, PhD

Professor of Kinesiology, Physiology, and Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Noll Laboratory

University Park, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

10736

Identifier Type: -

Identifier Source: org_study_id