Study Stopped
Study funding ended prior to completion.
Angiotensin-(1-7) in Peripheral Arterial Disease
Protective Effects of Angiotensin-(1-7) in Peripheral Arterial Disease
1 other identifier
interventional
6
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for early_phase_1
Started Sep 2017
Typical duration for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 2, 2017
CompletedFirst Posted
Study publicly available on registry
August 4, 2017
CompletedStudy Start
First participant enrolled
September 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 9, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 9, 2020
CompletedMay 3, 2024
May 1, 2024
2.5 years
August 2, 2017
May 2, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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 Outcomes (2)
Blood Pressure
50 minutes
Heart Rate
50 minutes
Other Outcomes (3)
Renin-Angiotensin System Hormones
50 minutes
Nitric Oxide Bioavailability
50 minutes
Lipids
50 minutes
Study Arms (2)
Angiotensin-(1-7)
EXPERIMENTALSubjects 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.
Saline
PLACEBO COMPARATORSubjects 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.
Interventions
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.
Normal saline will be used as the placebo comparator.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Amy C Arnold, PhD
Penn State College of Medicine
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor
Study Record Dates
First Submitted
August 2, 2017
First Posted
August 4, 2017
Study Start
September 1, 2017
Primary Completion
March 9, 2020
Study Completion
March 9, 2020
Last Updated
May 3, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will not share