Angiotensin-(1-7) in Peripheral Arterial Disease

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Milton S. Hershey Medical Center
• Treatments: Angiotensin I (1-7); Angiotensin II; Angiotensinogen

Criteria

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