An Early Phase 1 interventional study of Angiotensin 1-7 and Saline in Peripheral Arterial Disease, sponsored by Milton S. Hershey Medical Center. Terminated at 1 site in United States. Open to participants aged 21 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-05-03.
Sponsored by Milton S. Hershey Medical Center · Early Phase 1, Interventional, and Treatment
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.
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.
1,542 studies on the registry are indexed under Peripheral Arterial Disease; 282 are open to participants now.
This study's enrollment of 6 is below the median of 74 across 1,066 interventional studies indexed under Peripheral Arterial Disease.
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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.
Drug: Angiotensin 1-7
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.
Drug: Saline
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.
Also known as: Angiotensin I (1-7), Angiotensin I/II (1-7) Acetate
Normal saline will be used as the placebo comparator.
Also known as: normal saline, 0.9% sodium chloride
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.
Time frame: 50 minutes
Inflammatory Markers
The change in blood levels of inflammatory markers C-Reactive Protein and Interleukin-6 following angiotensin-(1-7) versus saline infusion.
Time frame: 50 minutes
Blood Pressure
The change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion.
Time frame: 50 minutes
Heart Rate
The change in heart rate following angiotensin-(1-7) versus saline infusion.
Time frame: 50 minutes
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.
Time frame: 50 minutes
Nitric Oxide Bioavailability
The change in circulating levels of nitrate and nitrite following angiotensin-(1-7) versus saline infusion.
Time frame: 50 minutes
Lipids
The change in circulating lipids (e.g. cholesterol, triglycerides) following angiotensin-(1-7) versus saline infusion.
Time frame: 50 minutes
Plan to share: No
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This study is terminated, as verified in May 2024. You cannot join it, but the record below documents what was studied.
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Milton S. Hershey Medical Center