AgingEarly Phase 1NCT04181606
Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion
A Early Phase 1 study testing Esmolol infusion, Saline infusion and Pre exercise baseline in people with Aging, run by David N. Proctor, PhD at 1 site in United States.
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 Read more about this study
- Who is it for?
- Ages 18 to 75 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Esmolol infusion, Saline infusion and Pre exercise baseline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2022to 25 Apr 2023
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
3.1 Inclusion Criteria
- 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
3.2 Exclusion Criteria
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
Trial locations and contacts
1 site in 1 country.
United States1 site
Noll Laboratory
University Park, Pennsylvania, 16803
About this study
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
Read the 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
- Being tested
- Esmolol infusion, Saline infusion, Pre exercise baseline, Isometric handgrip exercise, Semi-recumbent cycling
- Keywords
- Esmolol hydrochloride, Exercise
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esmolol infusionDrug
Also called Esmolol Hydrochloride
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 infusionDrug
Also called Normal saline solution
Saline will be rate/volume matched to the calculated esmolol dose.
Pre exercise baselineOther
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 exerciseOther
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 cyclingOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Saline infusion; Other: Pre exercise baseline; Other: Isometric handgrip exercise; Other: Semi-recumbent cycling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Secondary outcomes (9)
Tissue Saturation Index - Inactive Forearm Muscle
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
Measured: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Systolic Blood Pressure
Systolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Measured: At rest and 3 minutes into moderate exercise and heavy exercise.
Heart Rate
Heart rate recorded via EKG
Measured: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Cardiac Output
Cardiac Output recorded using bioimpedance cardiography
Measured: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Diastolic Blood Pressure
Diastolic Blood Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Measured: At rest and 3 minutes into moderate exercise and heavy exercise.
Mean Arterial Pressure
Mean Arterial Pressure recorded via an automatic sphygmomanometer (SunTech Tango)
Measured: At rest and 3 minutes into moderate exercise and heavy exercise.
Stroke Volume
Stroke Volume recorded using bioimpedance cardiography
Measured: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Systemic Vascular Conductance
Systemic Vascular Conductance recorded using bioimpedance cardiography
Measured: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
∆HHb - Inactive Forearm
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.
Measured: Last 60 seconds of Moderate and Heavy Exercise
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2019
- Study start2 Feb 2022
- Primary completion25 Apr 2023
- Study completion25 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- David N. Proctor, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David N. Proctor, PhD, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04181606
- Sponsor's protocol ID
- 10736
- Status last verified
- Apr 2025
- First submitted
- 26 Nov 2019
- Last updated
- 13 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion
- ClinicalTrials.gov ID
- NCT04181606
- Acronym / sponsor ID
- 10736
- Conditions
- Aging
- Keywords
- Esmolol hydrochloride, Exercise
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- David N. Proctor, PhDUniversity, hospital or other
- Study start
- 2 Feb 2022 (actual)
- Primary completion
- 25 Apr 2023 (actual)
- Study completion
- 25 Apr 2023 (actual)
- First posted
- 29 Nov 2019 (actual)
- Results
- Posted 13 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esmolol Infusion | Active comparator | Drug: Esmolol infusion, Other: Pre exercise baseline, Other: Isometric handgrip exercise, Other: Semi-recumbent cyclingDrug: 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. |
| Saline Infusion | Placebo comparator | Drug: Saline infusion, Other: Pre exercise baseline, Other: Isometric handgrip exercise, Other: Semi-recumbent cyclingSaline infusion volume/rate matched to the calculated dose of esmolol. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esmolol infusionAlso: Esmolol HydrochlorideThe 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). | Drug | Esmolol Infusion |
| Saline infusionAlso: Normal saline solutionSaline will be rate/volume matched to the calculated esmolol dose. | Drug | Saline Infusion |
| Pre exercise baselineSubject rests quietly while drug infusion begins (3 min loading dose followed by 10 min of maintenance dose) until heart rate and blood pressure stabilize. | Other | Esmolol Infusion, Saline Infusion |
| Isometric handgrip exerciseThe subject will grip at 40% of their maximum and maintain that grip for 90 seconds. Once at rest and once during heavy intensity cycling. | Other | Esmolol Infusion, Saline Infusion |
| Semi-recumbent cyclingSubjects 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. | Other | Esmolol Infusion, Saline Infusion |
Primary outcome
Tissue Saturation Index (TSI) - Active Leg Muscle
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
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
9 secondary outcomes
Tissue Saturation Index - Inactive Forearm Muscle
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Systolic Blood Pressure
Time frame: At rest and 3 minutes into moderate exercise and heavy exercise.
Heart Rate
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Cardiac Output
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Diastolic Blood Pressure
Time frame: At rest and 3 minutes into moderate exercise and heavy exercise.
Mean Arterial Pressure
Time frame: At rest and 3 minutes into moderate exercise and heavy exercise.
Stroke Volume
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
Systemic Vascular Conductance
Time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.
∆HHb - Inactive Forearm
Time frame: Last 60 seconds of Moderate and Heavy Exercise
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Esmolol infusion, Saline infusion and Pre exercise baseline in people with Aging, run by David N. Proctor, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tissue Saturation Index (TSI) - Active Leg Muscle (time frame: Last 60 seconds of Rest, Moderate exercise, and Heavy Exercise.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2025.