HypertensionPhase 1NCT02245230

Cardiovascular Effects of Angiotensin (1-7) in Essential Hypertension

A Phase 1 study testing Angiotensin (1-7), Trimethaphan and Phenylephrine in people with Hypertension and Hypertension, Essential, run by Vanderbilt University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to better understand the cardiovascular effects of the vasodilatory peptide Angiotensin (1-7) in human hypertension. In this study, the investigators will test the hypothesis that systemic Angiotensin (1-7) infusion produces negligible effects with intact baroreceptors, and that the… Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Hypertension, Hypertension, Essential
What is being tested?: Angiotensin (1-7), Trimethaphan and Phenylephrine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteUnited States
Study dates: Jan 2015to Dec 2023
Phase: 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 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Males and females of all races between 18 and 60 years of age
Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg. This will allow us to include subjects with "pre-hypertension."
Able and willing to provide informed consent

Who cannot join

Pregnancy or breast feeding
Current smokers or history of heavy smoking (>2 packs/day)
History of alcohol or drug abuse
Previous allergic reaction to study medications
Evidence of type I or type II diabetes (i.e. fasting glucose >126 mg/dl, use of anti-diabetic medications)
Cardiovascular disease other than hypertension such as myocardial infarction within 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy

Show all 17Show fewer

History of serious cerebrovascular disease such as cerebral hemorrhage, stroke, or transient ischemic attack
History or presence of immunological or hematological disorders
Impaired hepatic function [aspartate amino transaminase (AST) and/or alanine amino transaminase (ALT) > 2.0 x upper limit of normal range]
Impaired renal function (serum creatinine >1.5 mg/dl)
Anemia (hemoglobin <13.5 g/dl in males or <12.5 g/dl in females)
Treatment with phosphodiesterase 5 inhibitors
Treatment with anticoagulants
Treatment with chronic systemic glucocorticoid therapy (more than 7 consecutive days in 1 month)
Treatment with any investigational drug in the 1 month preceding the study
Inability to give, or withdraw, informed consent
Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e. clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol)

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University
Nashville, Tennessee, 37232

Other trials in United States

About this study

Read the detailed description

Pharmacologic approaches to increase levels or actions of the vasodilatory peptide Angiotensin (1-7) are currently in development for the treatment of hypertension based on findings from animal studies. There are limited and contradictory clinical studies, however, and it is unclear if this peptide even contributes to blood pressure regulation in humans. The purpose of this study is to learn more about the cardiovascular effects of Angiotensin (1-7) in essential hypertension, and to examine interactions of this peptide with the autonomic nervous system for blood pressure regulation. The investigators propose that the difficulties in showing Angiotensin (1-7) cardiovascular effects in previous clinical studies relates to the buffering capacity of the baroreceptor reflex to prevent changes in blood pressure. In this study, the investigators will test the hypothesis that Angiotensin (1-7) produces negligible effects with intact baroreceptors, and that the cardiovascular effects of this peptide are unmasked following elimination of baroreflex buffering. To test this hypothesis, the investigators will examine the effects of acute intravenous Angiotensin (1-7) infusion on blood pressure in subjects with essential hypertension under intact conditions and following acute autonomic withdrawal with the ganglionic blocker trimethaphan. The primary outcome will be the decrease in systolic blood pressure produced by Angiotensin (1-7) infusion, with comparisons made between intact and blocked study days. As a secondary objective, the investigators will examine for changes in systemic hemodynamics and circulating hormones in response to the Angiotensin (1-7) infusion, to determine potential mechanisms underlying any changes in blood pressure.

Conditions: Hypertension, Hypertension, Essential
Being tested: Angiotensin (1-7), Trimethaphan, Phenylephrine
Keywords: Hypertension, Autonomic Nervous System, Renin-Angiotensin System, Angiotensin (1-7), Ganglionic Blockers, Trimethaphan, Blood Pressure, Hemodynamics
Medical subject headings: Hypertension, Essential Hypertension

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-(1-7), Angiotensin I (1-7)
Angiotensin (1-7) is a peptide produced by the body. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 20 ng/kg/min.
TrimethaphanDrug
Also called Trimethaphan Camsylate
Trimethaphan is a Nn-nicotinic receptor antagonist that blocks sympathetic and parasympathetic transmission at the level of the autonomic ganglia. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 5.0 mg/min.
PhenylephrineDrug
Also called Phenylephrine Hydrochloride
Phenylephrine is an alpha 1-adrenergic agonist. It will be administered as an acute intravenous infusion to restore blood pressure following trimethaphan with doses ranging from 0.1 to 0.5 ug/kg/min.

Study groups in NCT02245230
Study group	Role	What they receive
Intact Study Day	Active comparator	Subjects will receive saline infusion for 60 minutes followed by five ascending doses of Angiotensin (1-7) ranging from 0.5 to 20 ng/kg/min. Each dose will be maintained for 10 minutes with hemodynamic measurements and blood samples collected at the end of each dosing period. Receives: Drug: Angiotensin (1-7)
Autonomic Blockade Study Day	Experimental	Autonomic blockade will be induced by continuous intravenous infusion of trimethaphan starting at 0.5-1.0 mg/min and increasing by 1.0 mg/min every 2 to 6 minutes up to an infusion rate of 5 mg/min. Blood pressure will be restored to pre-trimethaphan levels with intravenous phenylephrine infusion at individually titrated doses, starting with 0.1 ug/kg/min. Angiotensin (1-7) will then be infused in five ascending doses ranging from 0.5 to 20 ng/kg/min. Each dose will be maintained for 10 minutes with hemodynamic measurements and blood samples collected at the end of each dosing period. Receives: Drug: Angiotensin (1-7); Drug: Trimethaphan; Drug: Phenylephrine

What is being measured

The primary outcome is the main question the study is designed to answer.

Systolic Blood Pressure
The primary outcome will be the change in systolic blood pressure from baseline produced by the Angiotensin (1-7) infusion, with comparisons made between intact and autonomic blockade study days.
Measured: Change from baseline in systolic blood pressure over the 50-minute infusion period

Secondary outcomes (2)

Hemodynamic Measures
We will examine for changes in cardiac output, stroke volume, and systemic vascular resistance to determine hemodynamic mechanisms underlying any changes in blood pressure during Angiotensin (1-7) infusion.
Measured: Change from baseline in hemodynamic measures over the 50-minute infusion period
Circulating Renin-Angiotensin System Components
We will examine for changes in plasma renin activity, angiotensin II, Angiotensin (1-7), and aldosterone levels to determine renin-angiotensin system hormonal mechanisms underlying any changes in blood pressure during Angiotensin (1-7) infusion.
Measured: Change from baseline in circulating renin-angiotensin system components over the 50-minute infusion period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2015Dec 2023

First posted19 Sep 2014 (estimated)
Study startJan 2015
Primary completionDec 2023
Study completionDec 2023

Why it stopped: We were not able to enroll adequate number of participants that met the inclusion/exclusion criteria, and we run out of funding.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HypertensionStudies 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: Phase 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02245230
Sponsor's protocol ID: 140958
Status last verified: Jan 2024
First submitted: 17 Sep 2014
Last updated: 9 Jan 2024
Results posted: No
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cardiovascular Effects of Angiotensin (1-7) in Essential Hypertension
ClinicalTrials.gov ID: NCT02245230
Acronym / sponsor ID: 140958
Conditions: Hypertension, Hypertension, Essential
Keywords: Hypertension, Autonomic Nervous System, Renin-Angiotensin System, Angiotensin (1-7), Ganglionic Blockers, Trimethaphan, Blood Pressure, Hemodynamics
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: We were not able to enroll adequate number of participants that met the inclusion/exclusion criteria, and we run out of funding.
Enrolment: 24 participants (actual)
Lead sponsor: Vanderbilt UniversityUniversity, hospital or other
Study start: Jan 2015 (actual)
Primary completion: Dec 2023 (actual)
Study completion: Dec 2023 (actual)
First posted: 19 Sep 2014 (estimated)
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.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Intact Study Day	Active comparator	Drug: Angiotensin (1-7)Subjects will receive saline infusion for 60 minutes followed by five ascending doses of Angiotensin (1-7) ranging from 0.5 to 20 ng/kg/min. Each dose will be maintained for 10 minutes with hemodynamic measurements and blood samples collected at the end of each dosing period.
Autonomic Blockade Study Day	Experimental	Drug: Angiotensin (1-7), Drug: Trimethaphan, Drug: PhenylephrineAutonomic blockade will be induced by continuous intravenous infusion of trimethaphan starting at 0.5-1.0 mg/min and increasing by 1.0 mg/min every 2 to 6 minutes up to an infusion rate of 5 mg/min. Blood pressure will be restored to pre-trimethaphan levels with intravenous phenylephrine infusion at individually titrated doses, starting with 0.1 ug/kg/min. Angiotensin (1-7) will then be infused in five ascending doses ranging from 0.5 to 20 ng/kg/min. Each dose will be maintained for 10 minutes with hemodynamic measurements and blood samples collected at the end of each dosing period.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (3 listed)

Males and females of all races between 18 and 60 years of age
Hypertension defined by two or more properly measured seated blood pressure readings >130/85 mmHg. This will allow us to include subjects with "pre-hypertension."
Able and willing to provide informed consent

Key exclusion criteria (17 listed)

Pregnancy or breast feeding
Current smokers or history of heavy smoking (>2 packs/day)
History of alcohol or drug abuse
Previous allergic reaction to study medications
Evidence of type I or type II diabetes (i.e. fasting glucose >126 mg/dl, use of anti-diabetic medications)

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-(1-7), Angiotensin I (1-7)Angiotensin (1-7) is a peptide produced by the body. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 20 ng/kg/min.	Drug	Autonomic Blockade Study Day, Intact Study Day
TrimethaphanAlso: Trimethaphan CamsylateTrimethaphan is a Nn-nicotinic receptor antagonist that blocks sympathetic and parasympathetic transmission at the level of the autonomic ganglia. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 5.0 mg/min.	Drug	Autonomic Blockade Study Day
PhenylephrineAlso: Phenylephrine HydrochloridePhenylephrine is an alpha 1-adrenergic agonist. It will be administered as an acute intravenous infusion to restore blood pressure following trimethaphan with doses ranging from 0.1 to 0.5 ug/kg/min.	Drug	Autonomic Blockade Study Day

Primary outcome

Systolic Blood Pressure
Time frame: Change from baseline in systolic blood pressure over the 50-minute infusion period
The primary outcome will be the change in systolic blood pressure from baseline produced by the Angiotensin (1-7) infusion, with comparisons made between intact and autonomic blockade study days.

2 secondary outcomes

Hemodynamic Measures
Time frame: Change from baseline in hemodynamic measures over the 50-minute infusion period
Circulating Renin-Angiotensin System Components
Time frame: Change from baseline in circulating renin-angiotensin system components over the 50-minute infusion period

Results and safety

The study was stopped early (reason given: We were not able to enroll adequate number of participants that met the inclusion/exclusion criteria, and we run out of funding.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2024.
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.

Italo Biaggioni, MD principal investigator

Vanderbilt University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Angiotensin (1-7), Trimethaphan and Phenylephrine in people with Hypertension and Hypertension, Essential, run by Vanderbilt University 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 3 inclusion and 17 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 9 Jan 2024. 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. 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?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

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?

Systolic Blood Pressure (time frame: Change from baseline in systolic blood pressure over the 50-minute infusion period). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02245230.

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 9 Jan 2024.