Angiotensin-(1-7) and Energy Expenditure in Human Obesity

NCT ID: NCT03777215

Last Updated: 2025-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-26
• Study Completion Date: 2026-12-31

Brief Summary

The objective of this study is to better define the role of the hormone angiotensin-(1-7) in energy balance. We will test the overall hypothesis that angiotensin-(1-7) increases resting energy expenditure and promotes markers of heat production (thermogenesis) in white adipose tissue in human obesity.

Detailed Description

Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to produce positive cardiovascular and metabolic effects in animal models. In this study, the investigators will determine if angiotensin-(1-7) can increase resting energy expenditure and promote white adipose tissue heat production (thermogenesis) in obese human subjects. The investigators will perform a randomized, double-blind, two-arm parallel group study to determine effects of acute intravenous angiotensin-(1-7) versus saline infusion on resting energy expenditure measured by indirect calorimetry in obese human participants. In addition, blood pressure and heart rate will be measured and blood samples obtained to measure for changes in circulating renin-angiotensin system and metabolic hormones. Abdominal subcutaneous white adipose biopsies will also be obtained from obese human participants during acute angiotensin-(1-7) versus saline infusions to examine for changes in gene expression for markers of thermogenesis. The findings from these studies will advance understanding of hormonal mechanisms involved in the etiology of obesity, and provide new insight into the potential for targeting angiotensin-(1-7) to improve energy balance in human obesity.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

Angiotensin-(1-7)

Subjects will receive intravenous infusion of three ascending doses of angiotensin-(1-7). The doses are: 2, 4, and 8 ng/kg/min. Each dose will be maintained for 10 minutes, with the highest dose maintained for an additional 90 minutes. The total infusion period is 120 minutes.

Group Type: EXPERIMENTAL

Angiotensin-(1-7)

Intervention Type: DRUG

This is a biologically active beneficial hormone of the renin-angiotensin system.

Placebo

Subjects will receive intravenous infusion of saline that is matched in volume to the angiotensin-(1-7). The total infusion period is 120 minutes.

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 beneficial hormone of the renin-angiotensin system.

Intervention Type: DRUG

Saline

Saline will be used as the placebo comparator.

Intervention Type: DRUG

Other Intervention Names

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

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
• Satisfactory history and physical exam

Exclusion Criteria

• Age ≤ 17 or ≥ 61 years
• Pregnant, nursing, or postmenopausal women
• Decisional impairment
• Prisoners
• Alcohol or drug abuse
• Current smokers
• Highly trained athletes
• Claustrophobia
• 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 other than hypertension (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 or alanine aminotransferase levels >2 times upper limit of normal range)
• Impaired renal function (serum creatinine >2.0 mg/dl)
• Anemia
• Treatment with anticoagulants (e.g. warfarin)
• Treatment with chronic systemic glucocorticoid therapy (>7 consecutive days in 1 month)
• Treatment with medications influencing energy expenditure (e.g. psychostimulants)
• 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

Amy Arnold

OTHER

Sponsor Role: lead

Responsible Party

Amy Arnold

Associate Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amy C Arnold, PhD

Role: PRINCIPAL_INVESTIGATOR

Pennsylvania State University College of Medicine

Locations

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

Other Identifiers

9895

Identifier Type: -

Identifier Source: org_study_id