Angiotensin-(1-7) in Peripheral Arterial Disease

Peripheral Arterial Disease Clinical Trial

Official title:

Protective Effects of Angiotensin-(1-7) in Peripheral Arterial Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03240068
• Other study ID #: 6189
• Status: Terminated
• Phase: Early Phase 1
• Start date: September 1, 2017
• Est. completion date: March 9, 2020

Study information

• Verified date: May 2024
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Peripheral arterial disease (PAD) affects over 8 million individuals in the United States alone. This is a form of atherosclerosis in which plaques preferentially build up inside the arteries of the legs to limit blood flow. These patients are at high risk for heart attack and stroke, with at least half dying from coronary artery disease. Our understanding of the causes of PAD remains incomplete. The renin-angiotensin hormone system is one mechanism known to contribute to atherosclerosis. Pharmacologic blockade of the hormone angiotensin II is beneficial in forms of atherosclerosis, including peripheral arterial disease, to improve blood vessel damage and functional outcomes. These therapies also increase circulating levels of angiotensin-(1-7), a hormone that dilates blood vessels. Angiotensin-(1-7) improves blood vessel function and reduces inflammation to protect against atherosclerosis in animal models; however, there are no clinical data in patients with atherosclerosis. The overall goal of this project is to examine the cardiovascular effects of angiotensin-(1-7) in PAD.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: March 9, 2020
• Est. primary completion date: March 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• Angiotensin 1-7
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.
• Saline
Normal saline will be used as the placebo comparator.

Locations

Country	Name	City	State
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Renin-Angiotensin System Hormones	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.	50 minutes
Other	Nitric Oxide Bioavailability	The change in circulating levels of nitrate and nitrite following angiotensin-(1-7) versus saline infusion.	50 minutes
Other	Lipids	The change in circulating lipids (e.g. cholesterol, triglycerides) following angiotensin-(1-7) versus saline infusion.	50 minutes
Primary	Leg Blood Flow	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.	50 minutes
Primary	Inflammatory Markers	The change in blood levels of inflammatory markers C-Reactive Protein and Interleukin-6 following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Blood Pressure	The change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion.	50 minutes
Secondary	Heart Rate	The change in heart rate following angiotensin-(1-7) versus saline infusion.	50 minutes