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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03777215
• Other study ID #: 9895
• Status: Recruiting
• Phase: Early Phase 1
• Start date: September 26, 2019
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Milton S. Hershey Medical Center
• Contact: Aimee C Cauffman, BSN
• Phone: 717-531-1617
• Email: acauffman[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Angiotensin-(1-7)
This is a biologically active beneficial hormone of the renin-angiotensin system.
• Saline
Saline will be used as the placebo comparator.

Locations

Country	Name	City	State
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Amy Arnold

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Skin temperature	Change in skin temperature following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Skin blood flow	Change in skin blood flow following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Abdominal heat production	Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Catecholamines	Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Insulin	Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Glucose	Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Fatty acids	Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Angiotensin II	Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Angiotensin-(1-7)	Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Renin	Change in plasma renin activity following angiotensin-(1-7) versus saline infusion	120 minutes
Other	Aldosterone	Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion	120 minutes
Primary	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
Primary	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	Blood pressure	Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion	120 minutes
Secondary	Heart rate	Change in heart rate following angiotensin-(1-7) versus saline infusion	120 minutes