Recruiting
Early Phase 1

Angiotensin-(1-7)

Sponsor:

Milton S. Hershey Medical Center

Code:

NCT05301192

Conditions

Aging

Eligibility Criteria

Sex: All

Age: 65 - 70+

Healthy Volunteers: Accepted

Interventions

Angiotensin-(1-7)

Saline

Study Details

Brief summary:

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.

Conditions

Aging

Study ID

NCT05301192

Start date

Dec 9, 2022

Status verified date

Sep, 2025

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 65 - 70+

Healthy Volunteers: Accepted

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 Design

Enrollment

26 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

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.

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.

Interventions

Angiotensin-(1-7)

This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.

Saline

Saline will be used as the placebo comparator.

Primary outcome measure

  • Change in Muscle Sympathetic Nerve Burst Rate [ Time Frame: 110 minutes ]

Central Contacts and Locations

Central contacts

Aimee Cauffman, RN

717-531-1617acauffman@pennstatehealth.psu.edu

Amy Arnold, PhD

717-531-3674aarnold5@pennstatehealth.psu.edu

Locations

Penn State Milton S. Hershey Medical Center

Recruiting

Hershey, Pennsylvania, United States, 17033

Contacts

Amy Arnold, PhD

717-531-3674aarnold5@pennstatehealth.psu.edu

More Information

Sponsor

Milton S. Hershey Medical Center

Last update posted

Sep 19, 2025

Last verified

Sep, 2025

Keywords

  • cardiovascular
  • blood pressure
  • autonomic nervous system
  • renin-angiotensin system
  • endothelial

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Milton S. Hershey Medical Center on 2025-09-19.