- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02245230
Cardiovascular Effects of Angiotensin (1-7) in Essential Hypertension
January 8, 2024 updated by: Italo Biaggioni, Vanderbilt University
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 cardiovascular effects of this peptide are unmasked following elimination of baroreflex buffering.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
24
Phase
- 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 Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University
-
-
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
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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)
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: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Intact Study Day
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.
|
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.
Other Names:
|
Experimental: Autonomic Blockade Study Day
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.
|
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.
Other Names:
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Change from baseline in systolic blood pressure over the 50-minute infusion period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hemodynamic Measures
Time Frame: Change from baseline in hemodynamic measures over the 50-minute infusion period
|
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.
|
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
|
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.
|
Change from baseline in circulating renin-angiotensin system components over the 50-minute infusion period
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Italo Biaggioni, MD, Vanderbilt University
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)
January 1, 2015
Primary Completion (Actual)
December 1, 2023
Study Completion (Actual)
December 1, 2023
Study Registration Dates
First Submitted
September 17, 2014
First Submitted That Met QC Criteria
September 18, 2014
First Posted (Estimated)
September 19, 2014
Study Record Updates
Last Update Posted (Actual)
January 9, 2024
Last Update Submitted That Met QC Criteria
January 8, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Hypertension
- Essential Hypertension
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Antagonists
- Cholinergic Agents
- Protective Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Cardiotonic Agents
- Adjuvants, Anesthesia
- Respiratory System Agents
- Sympathomimetics
- Vasoconstrictor Agents
- Mydriatics
- Ganglionic Blockers
- Nicotinic Antagonists
- Nasal Decongestants
- Adrenergic alpha-1 Receptor Agonists
- Angiotensin I (1-7)
- Trimethaphan
- Trimethaphan camsylate
- Phenylephrine
- Oxymetazoline
Other Study ID Numbers
- 140958
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
Clinical Trials on Hypertension
-
National Taiwan University Hospital Hsin-Chu BranchRecruitingHypertension,Essential | Hypertension, MaskedTaiwan
-
University of Alabama at BirminghamTroy UniversityCompletedHypertension | Hypertension, Resistant to Conventional Therapy | Uncontrolled Hypertension | Hypertension, White CoatUnited States
-
BayerCompletedPrimary HypertensionChina
-
Columbia UniversityAgency for Healthcare Research and Quality (AHRQ)Active, not recruitingWhite Coat Hypertension | Hypertension,EssentialUnited States
-
Addpharma Inc.Completed
-
Universidade Federal de Santa MariaCompletedHealthy Volunteers | Hypertension, EssentialBrazil
-
Sheffield Teaching Hospitals NHS Foundation TrustUniversity of SheffieldCompletedIdiopathic Pulmonary Arterial Hypertension | Chronic Thromboembolic Pulmonary HypertensionUnited Kingdom
-
China Academy of Chinese Medical SciencesGuang'anmen Hospital of China Academy of Chinese Medical SciencesCompletedHypertension, Resistant to Conventional Therapy | Primary HypertensionChina
-
Cytos Biotechnology AGCompletedMild Essential Hypertension | Moderate Essential HypertensionSwitzerland
Clinical Trials on Angiotensin (1-7)
-
University of ArizonaNational Heart, Lung, and Blood Institute (NHLBI); Suburban HospitalSuspendedCognitive Impairment | Coronary Artery Bypass SurgeryUnited States
-
Instituto de Cardiologia do Rio Grande do SulUnknown
-
Amy ArnoldAmerican Heart AssociationRecruiting
-
Milton S. Hershey Medical CenterNational Heart, Lung, and Blood Institute (NHLBI)Recruiting
-
Amy ArnoldRecruiting
-
University of ArizonaUnited States Department of DefenseNot yet recruiting
-
Rambam Health Care CampusConstant Therapeutics LLCRecruiting
-
US Biotest, Inc.Tarix PharmaceuticalsTerminatedHIV InfectionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedBone Cancer | Chondrosarcoma | Recurrent Osteosarcoma | Clear Cell Sarcoma of the Kidney | Metastatic Osteosarcoma | Ovarian Sarcoma | Recurrent Adult Soft Tissue Sarcoma | Recurrent Uterine Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage III Uterine Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage...United States
-
Erasme University HospitalFonds Erasme pour la Recherche MedicaleNot yet recruitingRespiratory Failure | SARS-CoV-2 | Coronavirus | Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere