Clinical trial NCT03777215: Angiotensin-(1-7) and Energy Expenditure in Human Obesity
Official title: Angiotensin-(1-7) and Energy Expenditure in Human Obesity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Obesity
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2018-12-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Resting energy expenditure
timeFrame: 120 minutes
measure: Uncoupling protein 1
timeFrame: 120 minutes
Secondary outcomes:
measure: Blood pressure
timeFrame: 120 minutes
measure: Heart rate
timeFrame: 120 minutes
Other outcomes:
measure: Skin temperature
timeFrame: 120 minutes
measure: Skin blood flow
timeFrame: 120 minutes
measure: Abdominal heat production
timeFrame: 120 minutes
measure: Catecholamines
timeFrame: 120 minutes
measure: Insulin
timeFrame: 120 minutes
measure: Glucose
timeFrame: 120 minutes
measure: Fatty acids
timeFrame: 120 minutes
measure: Angiotensin II
timeFrame: 120 minutes
measure: Angiotensin-(1-7)
timeFrame: 120 minutes
measure: Renin
timeFrame: 120 minutes
measure: Aldosterone
timeFrame: 120 minutes
Locations:
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Pennsylvania State University College of Medicine
name: Amy C Arnold, PhD
role: PRINCIPAL_INVESTIGATOR
References: