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

• Sponsor: Amy Arnold (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03777215
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 47.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Angiotensin-(1-7); Drug: Saline	Early Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Angiotensin-(1-7) and Energy Expenditure in Human Obesity
• Actual Study Start Date: Sep 26, 2019
• Anticipated Primary Completion Date: Sep 1, 2023
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

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: 0.9% sodium chloride normal saline

Outcome Measures

Primary Outcome Measures

1. Resting energy expenditure [120 minutes]

   Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.

2. Uncoupling protein 1 [120 minutes]

   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.

Secondary Outcome Measures

1. Blood pressure [120 minutes]

   Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion

2. Heart rate [120 minutes]

   Change in heart rate following angiotensin-(1-7) versus saline infusion

Other Outcome Measures

1. Skin temperature [120 minutes]

   Change in skin temperature following angiotensin-(1-7) versus saline infusion

2. Skin blood flow [120 minutes]

   Change in skin blood flow following angiotensin-(1-7) versus saline infusion

3. Abdominal heat production [120 minutes]

   Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion

4. Catecholamines [120 minutes]

   Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion

5. Insulin [120 minutes]

   Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion

6. Glucose [120 minutes]

   Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion

7. Fatty acids [120 minutes]

   Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion

8. Angiotensin II [120 minutes]

   Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion

9. Angiotensin-(1-7) [120 minutes]

   Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion

10. Renin [120 minutes]

    Change in plasma renin activity following angiotensin-(1-7) versus saline infusion

11. Aldosterone [120 minutes]

    Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033

Sponsors and Collaborators

• Amy Arnold

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Amy Arnold, Assistant Professor, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT03777215
• Other Study ID Numbers: 00009895
• First Posted: Dec 17, 2018
• Last Update Posted: Jun 3, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Obesity; Angiotensin I (1-7)

Study Results

No Results Posted as of Jun 3, 2022