- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03240068
Angiotensin-(1-7) in Peripheral Arterial Disease
Protective Effects of Angiotensin-(1-7) in Peripheral Arterial Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a randomized, double blind, placebo-controlled, crossover study to determine if acute intravenous Ang-(1-7) infusion can reduce systemic inflammation and improve measures of leg blood flow in subjects with PAD. The investigators will also measure for changes in blood pressure and circulating hormones in response to angiotensin-(1-7) infusion. This is an outpatient study that will be conducted in the Clinical Research Center at the Penn State Milton S. Hershey Medical Center.
Subjects with PAD will participate in a screening visit, and if eligible, in two separate study visits in which they will receive intravenous angiotensin-(1-7) or saline infusion. Each study visit will last approximately 4 hours, with at least one week of washout between study visits. During study visits, subjects will be instrumented with two intravenous catheters (one for drug infusion and one for blood sampling), arm and finger blood pressure cuffs, sticky patches to measure heart rate, a belt around the stomach to measure breathing, an ultrasound probe on each leg to measure blood flow, a probe on the ear to measure blood oxygen saturation, a probe on each calf muscle to measure oxygen levels, and probes on the skin to measure temperature and blood flow. The investigators will obtain baseline measures of blood pressure and heart rate and collect blood samples to measure hormones in the blood. After baseline measurements, the investigators will infuse angiotensin-(1-7) or saline for 50 minutes. Finger cuff blood pressure, leg blood flow, and calf muscle oxygen levels will be measured continuously during infusions. The investigators will measure blood pressure and heart rate and collect blood samples at the end of the infusion period.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Penn State Milton S. Hershey Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Sex: Male or Female
- Age: 21-80 years of age
- Diagnosed with PAD (e.g. ankle-brachial index below 0.9)
- Fontaine stage II or less (no rest pain)
- Capable of giving informed consent
- Fluent in written and spoken English
Exclusion Criteria:
- Age less than or equal to 20 years or greater than or equal to 81 years
- Pregnant or nursing woman
- Decisional impairment
- Prisoners
- Alcohol or drug abuse
- Evidence of type I or type II diabetes (fasting glucose >126 mg/dl or use of anti-diabetic medications)
- 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 disease
- Impaired hepatic function [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 2 times the upper limit of normal range)
- Impaired renal function (serum creatinine >2.0 mg/dl)
- Anemia
- Treatment with serotonin-norepinephrine reuptake inhibitors (SNRI) or norepinephrine transporter (NET) inhibitors
- Treatment with phosphodiesterase-5 inhibitors
- Treatment with anticoagulants
- Treatment with chronic systemic glucocorticoid therapy (>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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Angiotensin-(1-7)
Subjects will receive intravenous infusion of five ascending doses of angiotensin-(1-7).
The doses are: 1, 2, 4, 8, and 12 ng/kg/min.
Each dose will be maintained for 10 minutes, for a total infusion period of 50 minutes.
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This is a biologically active hormone of the renin-angiotensin system.
It may play a beneficial role in regulation of blood pressure by dilating blood vessels and reducing inflammation.
Other Names:
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Placebo Comparator: Saline
Subjects will receive intravenous infusion of saline that is matched in volume to the angiotensin-(1-7) arm.
Saline infusion will be maintained for a total infusion period of 50 minutes.
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Normal saline will be used as the placebo comparator.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Leg Blood Flow
Time Frame: 50 minutes
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The change in measures of leg blood flow (e.g.
femoral blood flow and conductance, calf muscle oxygen saturation) following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Inflammatory Markers
Time Frame: 50 minutes
|
The change in blood levels of inflammatory markers C-Reactive Protein and Interleukin-6 following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood Pressure
Time Frame: 50 minutes
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The change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Heart Rate
Time Frame: 50 minutes
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The change in heart rate following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renin-Angiotensin System Hormones
Time Frame: 50 minutes
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The change in circulating levels of renin-angiotensin system hormones (e.g.
plasma renin activity, angiotensin peptides, aldosterone) following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Nitric Oxide Bioavailability
Time Frame: 50 minutes
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The change in circulating levels of nitrate and nitrite following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Lipids
Time Frame: 50 minutes
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The change in circulating lipids (e.g.
cholesterol, triglycerides) following angiotensin-(1-7) versus saline infusion.
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50 minutes
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Amy C Arnold, PhD, Penn State College of Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Atherosclerosis
- Peripheral Arterial Disease
- Peripheral Vascular Diseases
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Vasodilator Agents
- Enzyme Inhibitors
- Protease Inhibitors
- Serine Proteinase Inhibitors
- Vasoconstrictor Agents
- Angiotensin I (1-7)
- Angiotensin II
- Angiotensinogen
Other Study ID Numbers
- 6189
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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