Angiotensin 1-7 in Obesity Hypertension

NCT ID: NCT03604289

Last Updated: 2024-06-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2023-06-03

Brief Summary

The purpose of this study is to find out if the investigational drug angiotensin-(1-7) improves cardiovascular health in patients with obesity and high blood pressure.

Detailed Description

Obesity is a major public health concern that greatly increases risk for developing cardiovascular disease. Importantly, obesity is associated with endothelial dysfunction and elevated sympathetic tone, vascular and autonomic derangements known to elevate blood pressure and increase cardiovascular risk. The renin-angiotensin system may explain cardiovascular complications in obesity. Angiotensin-(1-7) is a beneficial hormone that is reduced in obesity and restoration of this hormone improves endothelial function and reduces sympathetic activity in animal models, which may contribute to its blood pressure-lowering effects. The investigators will test the hypothesis that angiotensin-(1-7) improves cardiovascular function in humans with obesity hypertension. This hypothesis will be tested in a randomized, double blind, placebo-controlled crossover study. The investigators will measure the effects of acute intravenous angiotensin-(1-7) infusion on endothelial-mediated vasodilation in the brachial and coronary arteries and on blood pressure and muscle sympathetic nerve activity with direct microneurography recordings in obese hypertensive humans.

Conditions

Obesity; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Angiotensin-(1-7)

Participants receive intravenous angiotensin-(1-7) at one study visit for 100 minutes total. Angiotensin-(1-7) will be given in escalating doses of 2ng/kg/min, 4ng/kg/min, and 8ng/kg/min. Each of these doses will be infused for 10 minutes. Following the dose escalation, angiotensin-(1-7) will be given at 8ng/kg/min for an additional 70 minutes. Infusion rates will be calculated for each patient based on body mass.

Group Type: EXPERIMENTAL

Angiotensin-(1-7)

Intervention Type: DRUG

This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.

Saline

Participants receive intravenous saline at one study visit for 100 minutes total. 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. Saline will be given in escalating doses for 10 minutes each and then held for 70 minutes at the highest dose.

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Saline will be used as the placebo comparator

Interventions

Angiotensin-(1-7)

This is a biologically active endogenous angiotensin peptide that may play an important role in regulation of blood pressure.

Intervention Type: DRUG

Saline

Saline will be used as the placebo comparator

Intervention Type: DRUG

Other Intervention Names

Angiotensin I/II (1-7) Acetate; Normal saline; 0.9% sodium chloride

Eligibility Criteria

Inclusion Criteria

• Men and women of all races
• Capable of giving informed consent
• Age 18-60 years
• Body mass index (BMI) between 30-40 kg/m2
• Hypertension defined as two or more seated blood pressure readings >130/80 mmHg or use of anti-hypertensive medications
• Satisfactory history and physical exam

Exclusion Criteria

• Age ≤ 17 or ≥ 61 years
• Pregnant or nursing women
• Decisional impairment
• Prisoners
• Alcohol or drug abuse
• Current smokers
• Highly trained athletes
• Subjects with >5% weight change in the past 3 months
• 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 (AST or ALT levels >2 times upper limit of normal range)
• Impaired renal function (serum creatinine >2.0 mg/dl)
• Anemia
• Treatment with serotonin-norepinephrine reuptake inhibitors (SNRIs) or norepinephrine transporter (NET) inhibitors
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

Amy Arnold

OTHER

Sponsor Role: lead

Responsible Party

Amy Arnold

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amy C Arnold, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Penn State College of Medicine

Locations

Penn State College of Medicine

Hershey, Pennsylvania, United States

Countries

United States

Other Identifiers

18POST33960087

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

STUDY00008170

Identifier Type: -

Identifier Source: org_study_id