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

David N. Proctor, PhD

Status and phase: Completed; Early Phase 1

Conditions: Aging

Treatments: Drug: Esmolol infusion; Drug: Saline infusion; Other: Pre exercise baseline; Other: Isometric handgrip exercise; Other: Semi-recumbent cycling

Study type: Interventional

Funder types: Other

Identifiers

NCT04181606

10736

Details and patient eligibility

About

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

Full 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.

Enrollment: 30 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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 Clinical Research Center (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 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

11. 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

30 participants in 2 patient groups, including a placebo group

Esmolol Infusion

Active Comparator group

Description:

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.

Treatment:

Other: Semi-recumbent cycling

Other: Isometric handgrip exercise

Other: Pre exercise baseline

Drug: Esmolol infusion

Saline Infusion

Placebo Comparator group

Description:

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

Treatment:

Other: Semi-recumbent cycling

Other: Isometric handgrip exercise

Other: Pre exercise baseline

Drug: Saline infusion