Cardiovascular Effects of Angiotensin-(1-7) in Obesity Hypertension

Penn State Health

Status and phase: Enrolling; Early Phase 1

Conditions: Hypertension; Obesity

Treatments: Drug: Saline; Drug: Angiotensin-(1-7)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06482853

R01HL170140 (U.S. NIH Grant/Contract)

STUDY 8170-Part 2

Details and patient eligibility

About

Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.

Full description

A randomized, double blind, placebo controlled, crossover study will be conducted to determine if acute intravenous angiotensin-(1-7) infusion reduces cardiovascular sympathetic tone and blood pressure and improves the function of blood vessels in participants with obesity hypertension. This is an outpatient study that requires a screening visit, and if eligible, two study visits separated by at least one week in the Clinical Research Center within the Penn State Milton S. Hershey Medical Center. The study visits will include intravenous infusion of angiotensin-(1-7) or saline for approximately two hours, starting with increasing doses and holding at a steady-state dose. Endothelial function will be measured and blood samples collected at baseline and at the end of infusion. Blood pressure, heart rate, and muscle sympathetic nerve activity (via microneurography) will be measured continuously throughout the study. Each study visit will last approximately 4 hours.

Enrollment: 52 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Men and women of all races
• Age 18 to 65 years
• Body mass index (BMI) between 30-45 kg/m2
• Pre-hypertension (defined as two or more seated blood pressure readings >120/80 mmHg) or hypertension (defined as two or more seated blood pressure readings >130/80 mmHg or use of antihypertensive medications)
• Capable of giving informed consent
• Fluent in written and spoken English
• Satisfactory history and physical exam

Exclusion criteria

• Age ≤ 17 or ≥ 66 years
• Taking more than two antihypertensive medications
• Secondary causes of hypertension (e.g., pheochromocytoma, primary aldosteronism, aortic coarctation, adrenal disease)
• Pregnant or nursing women
• Women taking hormone replacement therapy within 6 months
• Decisional impairment
• Prisoners
• Alcohol or drug abuse
• Current smokers
• Highly trained athletes
• Subjects with >5% weight change in the past 3 months
• BMI > 45 kg/m2
• 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 disorders
• Impaired hepatic function [aspartate aminotransferase (AST) or alanine transaminase (ALT) levels >2 times upper limit of normal range]
• Impaired renal function (serum creatinine >2.0 mg/dl)
• Anemia
• Treatment with drugs increasing sympathetic activity [e.g., serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors, stimulants]
• Treatment with phosphodiesterase-5 inhibitors
• Treatment with anticoagulants (e.g. warfarin)
• 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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52 participants in 2 patient groups, including a placebo group

Angiotensin-(1-7)

Experimental group

Description:

Participants will receive intravenous angiotensin-(1-7) at one study visit for a total of 120 minutes. Angiotensin-(1-7) will be given in escalating doses of 2 ng/kg/min, 4 ng/kg/min, and 8 ng/kg/min. Each of these doses will be infused for 10 minutes. Following this 30 minute dose escalation period, angiotensin-(1-7) will be given at 8 ng/kg/min for an additional 90 minutes. Infusion rates will be calculated for each patient based on body mass.

Treatment:

Drug: Angiotensin-(1-7)

Saline

Placebo Comparator group

Description:

Participants receive intravenous saline at one study visit for a total of 120 minutes. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass.

Treatment:

Drug: Saline