AgingEarly Phase 1NCT05301192
Angiotensin-(1-7) Cardiovascular Effects in Aging
A Early Phase 1 study testing Angiotensin-(1-7) and Saline in people with Aging, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
Aging is an independent risk factor for developing hypertension and cardiovascular disease; however, the mechanisms underlying age-related cardiovascular disease remain poorly understood. Read more about this study
- Who is it for?
- Ages 65 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Angiotensin-(1-7) and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Dec 2022to 10 Jun 2024
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 65 to 80 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
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.
Read the 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.
- Conditions
- Aging
- Being tested
- Angiotensin-(1-7), Saline
- Keywords
- cardiovascular, blood pressure, autonomic nervous system, renin-angiotensin system, endothelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Angiotensin-(1-7)Drug
Also called Angiotensin I/II (1-7) Acetate
This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.
SalineDrug
Also called Normal saline, 0.9% sodium chloride
Saline will be used as the placebo comparator.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 110 minutes
Secondary outcomes (8)
Change in Muscle Sympathetic Nerve Burst Incidence
Muscle sympathetic nerve burst incidence will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Change in Muscle Sympathetic Nerve Amplitude
Muscle sympathetic nerve amplitude will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Change in Muscle Sympathetic Nerve Total Activity
Muscle sympathetic nerve total activity will be measured continuously using peroneal nerve microneurography during angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Change in Brachial Artery Diameter
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.
Measured: 110 minutes
Change in Systolic and Diastolic Blood Pressure
Blood pressure will be measured continuously with a finger and arm cuff during angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Change in Heart Rate
Heart rate will be measured continuously by electrocardiogram during angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Change in Heart Rate Variability
Heart rate variability will be calculated from the continuous electrocardiogram recordings obtained during angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Change in Plasma Catecholamines
Circulating catecholamine levels will be measured in blood samples obtained at baseline and at the end of angiotensin-(1-7) versus saline infusion.
Measured: 110 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2022
- Study start9 Dec 2022
- Primary completion10 Jun 2024
- Study completion10 Jun 2024
Why it stopped: Funding terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Amy Arnold, Milton S. Hershey Medical Center
- Investigators
- Amy Arnold, PhD, Principal investigator, Pennsylvania State University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05301192
- Sponsor's protocol ID
- STUDY 17401
- Other IDs
- K99HL159272
- Status last verified
- Sep 2026
- First submitted
- 17 Mar 2022
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Angiotensin-(1-7) Cardiovascular Effects in Aging
- ClinicalTrials.gov ID
- NCT05301192
- Acronym / sponsor ID
- STUDY 17401
- Conditions
- Aging
- Keywords
- cardiovascular, blood pressure, autonomic nervous system, renin-angiotensin system, endothelial
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding terminated
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 9 Dec 2022 (actual)
- Primary completion
- 10 Jun 2024 (actual)
- Study completion
- 10 Jun 2024 (actual)
- First posted
- 29 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Angiotensin-(1-7) | Experimental | Drug: 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. |
| Saline | Placebo comparator | Drug: SalineParticipants 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. |
Who may qualify
- Ages
- 65 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
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 |
|---|---|---|
| Angiotensin-(1-7)Also: Angiotensin I/II (1-7) AcetateThis is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure. | Drug | Angiotensin-(1-7) |
| SalineAlso: Normal saline, 0.9% sodium chlorideSaline will be used as the placebo comparator. | Drug | Saline |
Primary outcome
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.
8 secondary outcomes
Change in Muscle Sympathetic Nerve Burst Incidence
Time frame: 110 minutes
Change in Muscle Sympathetic Nerve Amplitude
Time frame: 110 minutes
Change in Muscle Sympathetic Nerve Total Activity
Time frame: 110 minutes
Change in Brachial Artery Diameter
Time frame: 110 minutes
Change in Systolic and Diastolic Blood Pressure
Time frame: 110 minutes
Change in Heart Rate
Time frame: 110 minutes
Change in Heart Rate Variability
Time frame: 110 minutes
Change in Plasma Catecholamines
Time frame: 110 minutes
Results and safety
The study was stopped early (reason given: Funding terminated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Amy Arnold, PhD principal investigator
Pennsylvania State University College of Medicine
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 Angiotensin-(1-7) and Saline in people with Aging, run by Milton S. Hershey Medical Center 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?
The sponsor lists 7 inclusion and 19 exclusion criteria. 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: stopped early, as of the sponsor's last update on 24 Sep 2026. 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?
The study was stopped early (reason given: Funding terminated). Results are not available in the source record.
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?
Change in Muscle Sympathetic Nerve Burst Rate (time frame: 110 minutes). 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 24 Sep 2026.