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

NCT04181606 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: 10736
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Aging

Keywords

Esmolol hydrochloride; Exercise

Outcome Measures

Primary Outcomes (1)

• Tissue Saturation Index (TSI) - Active Leg Muscle

  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

  Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.

Secondary Outcomes (9)

• Tissue Saturation Index - Inactive Forearm Muscle

  Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.

• Systolic Blood Pressure

  At rest and 3 minutes into moderate exercise and heavy exercise.

• Heart Rate

  Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.

• Cardiac Output

  Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.

• Diastolic Blood Pressure

  At rest and 3 minutes into moderate exercise and heavy exercise.

Study Arms (2)

Esmolol Infusion

ACTIVE COMPARATOR

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.

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

Saline Infusion

PLACEBO COMPARATOR

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

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

Interventions

Esmolol infusion 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).

Also known as: Esmolol Hydrochloride

Esmolol Infusion

Saline infusion DRUG

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

Also known as: Normal saline solution

Saline Infusion

Pre exercise baseline 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.

Esmolol Infusion; Saline Infusion

Isometric handgrip exercise 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.

Esmolol Infusion; Saline Infusion

Semi-recumbent cycling 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.

Esmolol Infusion; Saline Infusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving informed consent
• Premenopausal women ages 18-35 years OR post-menopausal women ages 55-70 years
• Satisfactory medical history and physical exam, as determined by a Clinical Research Center (CRC) clinician
• Not currently taking medications affecting heart rate or contractility
• Fluent in written and spoken English

You may not qualify if:

• Participants who will not be studied are those who:
• Are less than 19 years of age or more than 70 years of age
• Are pregnant or lactating
• Are prisoners or institutionalized individuals or unable to consent
• Diagnosed renal failure (Creatinine \>2.0 mg/dl)
• Diagnosed liver disease (ALT and aspartate aminotransferase {AST} 2 times normal)
• Diagnosed Reynaud's disease
• Have uncontrolled diabetes
• Have uncontrolled hypertension
• Have a left ventricular ejection fraction \< 40%
• Have a recent history of unstable angina or myocardial infarction (\<6 months), unstable angina, or use of nitrate medications within past 2 weeks
• \. 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

Sponsors & Collaborators

• David N. Proctor, PhD: lead

Study Sites (1)

Noll Laboratory

University Park, Pennsylvania, 16803, United States

Location

MeSH Terms

Conditions

Motor Activity

Interventions

esmolol; Saline Solution

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. David Proctor
• Organization: The Pennsylvania State University

dnp3@psu.edu

(814)863-0724

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants, investigators, and data analysts (outcomes assessors) will be blinded to the treatment (drug) order. The care providers (research nurse and physician) will be aware of the treatment order for safety reasons i.e., they will be assessing heart rate, blood pressure and symptoms before, during, and after the infusion.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Kinesiology, Physiology, and Medicine

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: November 29, 2019
• Study Start: February 2, 2022
• Primary Completion: April 25, 2023
• Study Completion: April 25, 2023
• Last Updated: May 13, 2025
• Results First Posted: May 13, 2025

Record last verified: 2025-04

Locations

US (1)