Angiotensin-(1-7) Cardiovascular Effects in Aging

September 18, 2025 updated by: Amy Arnold, Milton S. Hershey Medical Center
Aging is an independent risk factor for developing hypertension and cardiovascular disease; however, the mechanisms underlying age-related cardiovascular disease remain poorly understood. One hallmark of aging is an increase in sympathetic nervous system activity, which can decrease the number and/or sensitivity of β2 adrenergic receptors to reduce dilation of blood vessels and increase blood pressure. Identifying new targets to restore vascular β2 adrenergic receptor signaling may help reduce cardiovascular risk in aging. This study will test the hypothesis that angiotensin-(1-7), a protective hormone of the renin-angiotensin system, can reduce cardiovascular sympathetic outflow and blood pressure and improve endothelial function in older healthy humans.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A randomized, double blind, placebo-controlled, crossover study will be conducted to determine if acute intravenous angiotensin-(1-7) infusion can reduce cardiovascular sympathetic tone and blood pressure and improve the function of blood vessels in older healthy individuals. This is an outpatient study that requires a screening visit, and if eligible, two study visits separated by at least one week in the Clinical Research Center within the Penn State Milton S. Hershey Medical Center. The study visits will include intravenous infusion of angiotensin-(1-7) or saline for approximately two hours, starting with increasing doses and holding at a steady-state dose. Endothelial function will be measured and blood samples and endothelial cells collected at baseline and at the end of infusions. Blood pressure, heart rate, and muscle sympathetic nerve activity via microneurography will be measured throughout the study. Each study visit will last approximately 4 hours.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
26

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Penn State Milton S. Hershey Medical Center
        • Sub-Investigator:
          • Urs A Leuenberger, MD
        • Sub-Investigator:
          • Aimee Cauffman, RN
        • Sub-Investigator:
          • Cheryl Blaha, RN
        • Sub-Investigator:
          • Jian Cui, PhD
        • Contact:
        • Sub-Investigator:
          • Takuto Hamaoka, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 80 years (Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Men and women of all races and ethnicities
  • Capable of giving informed consent
  • Fluent in written and spoken English
  • Age 65-80 years
  • Body mass index (BMI) between 18.5 and 30 kg/m2
  • Normotensive defined as seated blood pressure <130/80 mmHg and without hypertensive medications
  • Satisfactory history and physical exam

Exclusion Criteria:

  • Age < 65 or > 80 years
  • Women who are pregnant, nursing, or taking hormone replacement therapy
  • Decisional impairment
  • Prisoners
  • Current or recent (less than 6 months) recreational drug history or excessive alcohol abuse history (greater than 14 drinks per week)
  • Current smokers
  • Highly trained athletes
  • Evidence of type I or type II diabetes (fasting glucose > 126 mg/dL or use of anti-diabetic medications)
  • Hypertension or history of serious cardiovascular disease (e.g., myocardial infarction within 6 months, symptomatic coronary artery disease, presence of angina pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g., cerebral hemorrhage, stroke, transient ischemic attack).
  • History or presence of immunological or hematological disorders
  • Impaired hepatic function [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >2 times upper limit of normal range]
  • Impaired renal function (serum creatinine >2.0 mg/dl)
  • Anemia
  • Taking drugs known to influence sympathetic activity (e.g. serotonin-norepinephrine reuptake inhibitors, norepinephrine transporter inhibitors, stimulants).
  • Treatment with anticoagulants (e.g. warfarin)
  • Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month in the 1-month preceding the study)
  • Treatment with any investigational drug in the 1-month preceding the study
  • Known allergy or contraindication to angiotensin converting enzyme inhibitors or angiotensin receptor blockers, both of which increase endogenous angiotensin-(1-7) levels as part of their mechanism of action
  • Inability to give, or withdraw, informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Angiotensin-(1-7)
Participants will receive intravenous angiotensin-(1-7) at one study visit for 110 minutes. Angiotensin-(1-7) will be given in escalating doses of 2 ng/kg/min, 4 ng/kg/min, and 8 ng/kg/min. Each of these doses will be infused for 10 minutes. Following the dose escalation, angiotensin-(1-7) will be given at 8 ng/kg/min for an additional 80 minutes. Infusion rates will be calculated for each participant based on body mass.
Drug: Angiotensin-(1-7)
This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
Other Names:
  • Angiotensin I/II (1-7) Acetate
Placebo Comparator: Saline
Participants will receive intravenous saline at one study visit for 110 minutes total. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each participant based on body mass.
Drug: Saline
Saline will be used as the placebo comparator.
Other Names:
  • Normal saline
  • 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Muscle Sympathetic Nerve Burst Rate
Time Frame: 110 minutes
Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
110 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Muscle Sympathetic Nerve Burst Incidence
Time Frame: 110 minutes
Muscle sympathetic nerve burst incidence will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Muscle Sympathetic Nerve Amplitude
Time Frame: 110 minutes
Muscle sympathetic nerve amplitude will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Muscle Sympathetic Nerve Total Activity
Time Frame: 110 minutes
Muscle sympathetic nerve total activity will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Brachial Artery Diameter
Time Frame: 110 minutes
A blood pressure cuff will be inflated to a suprasystolic pressure for 5 minutes then deflated. Brachial artery diameter will be measured continuously before, during, and after cuff inflation using duplex ultrasound at baseline and at the end of angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Systolic and Diastolic Blood Pressure
Time Frame: 110 minutes
Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Heart Rate
Time Frame: 110 minutes
Heart rate will be measured continuously by electrocardiogram during angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Heart Rate Variability
Time Frame: 110 minutes
Heart rate variability will be calculated from the continuous electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Plasma Catecholamines
Time Frame: 110 minutes
Circulating catecholamine levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
110 minutes

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Angiotensin II
Time Frame: 110 minutes
Plasma angiotensin II levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Angiotensin-(1-7)
Time Frame: 110 minutes
Plasma angiotensin-(1-7) levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Renin Activity
Time Frame: 110 minutes
Plasma renin activity will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
110 minutes
Change in Aldosterone
Time Frame: 110 minutes
Plasma or serum aldosterone levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
110 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Milton S. Hershey Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Amy Arnold, PhD, Pennsylvania State University College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 9, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 18, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 29, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 19, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY 17401
  • K99HL159272 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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