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

Primary Purpose

Obesity

Status

Recruiting

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Angiotensin-(1-7)

Saline

About this trial

This is an interventional other trial for Obesity

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Penn State Milton S. Hershey Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Angiotensin-(1-7)

Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Resting energy expenditure

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

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.

Secondary Outcome Measures

Blood pressure

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

Heart rate

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

Full Information

NCT ID

NCT03777215

First Posted

December 12, 2018

Last Updated

May 1, 2023

Sponsor

Amy Arnold

1. Study Identification

Unique Protocol Identification Number

NCT03777215

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 26, 2019 (Actual)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Amy Arnold

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Angiotensin-(1-7)

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Angiotensin-(1-7)

Other Intervention Name(s)

Angiotensin I/II (1-7) Acetate

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Saline

Other Intervention Name(s)

0.9% sodium chloride, normal saline

Intervention Description

Saline will be used as the placebo comparator.

Primary Outcome Measure Information:

Title

Resting energy expenditure

Description

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

Time Frame

120 minutes

Title

Uncoupling protein 1

Description

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.

Time Frame

120 minutes

Secondary Outcome Measure Information:

Title

Blood pressure

Description

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

Time Frame

120 minutes

Title

Heart rate

Description

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

Time Frame

120 minutes

Other Pre-specified Outcome Measures:

Title

Skin temperature

Description

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

Time Frame

120 minutes

Title

Skin blood flow

Description

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

Time Frame

120 minutes

Title

Abdominal heat production

Description

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

Time Frame

120 minutes

Title

Catecholamines

Description

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

Time Frame

120 minutes

Title

Insulin

Description

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

Time Frame

120 minutes

Title

Glucose

Description

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

Time Frame

120 minutes

Title

Fatty acids

Description

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

Time Frame

120 minutes

Title

Angiotensin II

Description

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

Time Frame

120 minutes

Title

Angiotensin-(1-7)

Description

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

Time Frame

120 minutes

Title

Renin

Description

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

Time Frame

120 minutes

Title

Aldosterone

Description

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

Time Frame

120 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Aimee C Cauffman, BSN

Phone

717-531-1617

acauffman@pennstatehealth.psu.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amy C Arnold, PhD

Organizational Affiliation

Pennsylvania State University College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Penn State Milton S. Hershey Medical Center

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Amy C Arnold, PhD

Phone

717-531-3674

aarnold5@pennstatehealth.psu.edu

First Name & Middle Initial & Last Name & Degree

Urs A Leuenberger, MD

First Name & Middle Initial & Last Name & Degree

Faisal Aziz, MD

First Name & Middle Initial & Last Name & Degree

John Radtka, MD

First Name & Middle Initial & Last Name & Degree

David N Proctor, PhD

First Name & Middle Initial & Last Name & Degree

Cheryl Blaha, RN

First Name & Middle Initial & Last Name & Degree

Aimee Cauffman, RN

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data will not be made available to other researchers.

Learn more about this trial

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

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