Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03777215
Recruitment Status : Recruiting
First Posted : December 17, 2018
Last Update Posted : December 14, 2021
Sponsor:
Information provided by (Responsible Party):
Amy Arnold, Milton S. Hershey Medical Center

Tracking Information
First Submitted Date  ICMJE December 12, 2018
First Posted Date  ICMJE December 17, 2018
Last Update Posted Date December 14, 2021
Actual Study Start Date  ICMJE September 26, 2019
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • Resting energy expenditure [ Time Frame: 120 minutes ]
    Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.
  • Uncoupling protein 1 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2018)
Energy expenditure [ Time Frame: 120 minutes ]
Change in energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • Blood pressure [ Time Frame: 120 minutes ]
    Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion
  • Heart rate [ Time Frame: 120 minutes ]
    Change in heart rate following angiotensin-(1-7) versus saline infusion
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2018)
  • Uncoupling Protein 1 [ Time Frame: 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.
  • Abdominal heat production [ Time Frame: 1 minute at baseline and end of infusion ]
    Change in abdominal heat production will be measured by infrared heat photographs taken at baseline and at end of angiotensin-(1-7) versus saline infusion.
  • Blood pressure [ Time Frame: 120 minutes ]
    Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion
  • Angiotensin II [ Time Frame: 120 minutes ]
    Change in circulating levels of angiotensin II measured at baseline and following angiotensin-(1-7) versus saline infusion.
  • Insulin [ Time Frame: 120 minutes ]
    Change in circulating levels of insulin at baseline and following angiotensin-(1-7) versus saline infusion.
  • Angiotensin-(1-7) [ Time Frame: 120 minutes ]
    Change in circulating levels of angiotensin-(1-7) measured at baseline and following angiotensin-(1-7) versus saline infusion.
  • Plasma Renin Activity [ Time Frame: 120 minutes ]
    Change in plasma renin activity measured at baseline and following angiotensin-(1-7) versus saline infusion.
  • Aldosterone [ Time Frame: 120 minutes ]
    Change in circulating levels of aldosterone measured at baseline and following angiotensin-(1-7) versus saline infusion.
  • Glucose [ Time Frame: 120 minutes ]
    Change in circulating levels of glucose measured at baseline and following angiotensin-(1-7) versus saline infusion.
  • Free Fatty Acids [ Time Frame: 120 minutes ]
    Change in circulating levels of free fatty acids measured at baseline and following angiotensin-(1-7) versus saline infusion.
Current Other Pre-specified Outcome Measures
 (submitted: April 18, 2019)
  • Skin temperature [ Time Frame: 120 minutes ]
    Change in skin temperature following angiotensin-(1-7) versus saline infusion
  • Skin blood flow [ Time Frame: 120 minutes ]
    Change in skin blood flow following angiotensin-(1-7) versus saline infusion
  • Abdominal heat production [ Time Frame: 120 minutes ]
    Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion
  • Catecholamines [ Time Frame: 120 minutes ]
    Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion
  • Insulin [ Time Frame: 120 minutes ]
    Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion
  • Glucose [ Time Frame: 120 minutes ]
    Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion
  • Fatty acids [ Time Frame: 120 minutes ]
    Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion
  • Angiotensin II [ Time Frame: 120 minutes ]
    Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion
  • Angiotensin-(1-7) [ Time Frame: 120 minutes ]
    Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion
  • Renin [ Time Frame: 120 minutes ]
    Change in plasma renin activity following angiotensin-(1-7) versus saline infusion
  • Aldosterone [ Time Frame: 120 minutes ]
    Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Angiotensin-(1-7) and Energy Expenditure in Human Obesity
Official Title  ICMJE Angiotensin-(1-7) and Energy Expenditure in Human Obesity
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Condition  ICMJE Obesity
Intervention  ICMJE
  • Drug: Angiotensin-(1-7)
    This is a biologically active beneficial hormone of the renin-angiotensin system.
    Other Name: Angiotensin I/II (1-7) Acetate
  • Drug: Saline
    Saline will be used as the placebo comparator.
    Other Names:
    • 0.9% sodium chloride
    • normal saline
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Angiotensin-(1-7)
  • 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.
    Intervention: Drug: Saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 14, 2018)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Aimee C Cauffman, BSN 717-531-1617 acauffman@pennstatehealth.psu.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03777215
Other Study ID Numbers  ICMJE 00009895
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Individual participant data will not be made available to other researchers.
Responsible Party Amy Arnold, Milton S. Hershey Medical Center
Study Sponsor  ICMJE Amy Arnold
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Amy C Arnold, PhD Pennsylvania State University College of Medicine
PRS Account Milton S. Hershey Medical Center
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP