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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Saline; Drug: Angiotensin-(1-7)

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Angiotensin-(1-7); This is a biologically active beneficial hormone of the renin-angiotensin system.; Other Names: Angiotensin I/II (1-7) Acetate
Placebo Comparator: 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.	Drug: Saline; Saline will be used as the placebo comparator.; Other Names: normal saline; 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting energy expenditure	Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.	120 minutes
Uncoupling protein 1	White adipose tissue biopsies will be taken at end of angiotensin-(1-7) versus saline infusion to assess gene expression of the heat producing (thermogenic) marker uncoupling protein 1.	120 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion	120 minutes
Heart rate	Change in heart rate following angiotensin-(1-7) versus saline infusion	120 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin temperature	Change in skin temperature following angiotensin-(1-7) versus saline infusion	120 minutes
Skin blood flow	Change in skin blood flow following angiotensin-(1-7) versus saline infusion	120 minutes
Abdominal heat production	Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion	120 minutes
Catecholamines	Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion	120 minutes
Insulin	Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion	120 minutes
Glucose	Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion	120 minutes
Fatty acids	Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion	120 minutes
Angiotensin II	Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion	120 minutes
Angiotensin-(1-7)	Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion	120 minutes
Renin	Change in plasma renin activity following angiotensin-(1-7) versus saline infusion	120 minutes
Aldosterone	Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion	120 minutes

Collaborators and Investigators

• Sponsor: Amy Arnold
• Investigators: Principal Investigator: Amy C Arnold, PhD, Pennsylvania State University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Organic Chemicals; Pharmaceutical Preparations; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Fatty Acids, Volatile; Sodium Compounds; Chlorides; Hydrochloric Acid; Saline Solution; Sodium Chloride; Acetates; angiotensin I (1-7)
• Other Study ID Numbers: 9895

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be made available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No