Angiotensin-(1-7) Cardiovascular Effects in Aging

NCT05301192 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY 17401K99HL159272
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in Muscle Sympathetic Nerve Burst Rate

  Muscle sympathetic nerve burst rate will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.

  110 minutes

Secondary Outcomes (8)

• Change in Muscle Sympathetic Nerve Burst Incidence

  110 minutes

• Change in Muscle Sympathetic Nerve Amplitude

  110 minutes

• Change in Muscle Sympathetic Nerve Total Activity

  110 minutes

• Change in Brachial Artery Diameter

  110 minutes

• Change in Systolic and Diastolic Blood Pressure

  110 minutes

Other Outcomes (4)

• Change in Angiotensin II

  110 minutes

• Change in Angiotensin-(1-7)

  110 minutes

• Change in Renin Activity

  110 minutes

Study Arms (2)

Angiotensin-(1-7)

EXPERIMENTAL

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)

Saline

PLACEBO COMPARATOR

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

Interventions

Angiotensin-(1-7) DRUG

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

Also known as: Angiotensin I/II (1-7) Acetate

Angiotensin-(1-7)

Saline DRUG

Saline will be used as the placebo comparator.

Also known as: Normal saline, 0.9% sodium chloride

Saline

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

MeSH Terms

Interventions

angiotensin I (1-7); Acetates; Sodium Chloride; Saline Solution

Intervention Hierarchy (Ancestors)

Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Amy Arnold, PhD

  Pennsylvania State University College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aimee Cauffman, RN

CONTACT

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

Amy Arnold, PhD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neural and Behavioral Sciences

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 29, 2022
• Study Start: December 9, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)