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

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ClinicalTrials.gov Identifier: NCT03777215
Recruitment Status : Recruiting
First Posted : December 17, 2018
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Amy Arnold, Milton S. Hershey Medical Center

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 26, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine


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 Name: 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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Blood pressure [ Time Frame: 120 minutes ]
    Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion

  2. Heart rate [ Time Frame: 120 minutes ]
    Change in heart rate following angiotensin-(1-7) versus saline infusion


Other Outcome Measures:
  1. Skin temperature [ Time Frame: 120 minutes ]
    Change in skin temperature following angiotensin-(1-7) versus saline infusion

  2. Skin blood flow [ Time Frame: 120 minutes ]
    Change in skin blood flow following angiotensin-(1-7) versus saline infusion

  3. Abdominal heat production [ Time Frame: 120 minutes ]
    Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion

  4. Catecholamines [ Time Frame: 120 minutes ]
    Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion

  5. Insulin [ Time Frame: 120 minutes ]
    Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion

  6. Glucose [ Time Frame: 120 minutes ]
    Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion

  7. Fatty acids [ Time Frame: 120 minutes ]
    Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion

  8. Angiotensin II [ Time Frame: 120 minutes ]
    Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion

  9. Angiotensin-(1-7) [ Time Frame: 120 minutes ]
    Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion

  10. Renin [ Time Frame: 120 minutes ]
    Change in plasma renin activity following angiotensin-(1-7) versus saline infusion

  11. Aldosterone [ Time Frame: 120 minutes ]
    Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03777215


Contacts
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Contact: Aimee C Cauffman, BSN 717-531-1617 acauffman@pennstatehealth.psu.edu

Locations
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United States, Pennsylvania
Penn State Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Amy C Arnold, PhD    717-531-3674    aarnold5@pennstatehealth.psu.edu   
Sub-Investigator: Urs A Leuenberger, MD         
Sub-Investigator: Faisal Aziz, MD         
Sub-Investigator: John Radtka, MD         
Sub-Investigator: David N Proctor, PhD         
Sub-Investigator: Cheryl Blaha, RN         
Sub-Investigator: Aimee Cauffman, RN         
Sponsors and Collaborators
Amy Arnold
Investigators
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Principal Investigator: Amy C Arnold, PhD Pennsylvania State University College of Medicine
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Responsible Party: Amy Arnold, Assistant Professor, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT03777215    
Other Study ID Numbers: 00009895
First Posted: December 17, 2018    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data will not be made available to other researchers.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Angiotensin I (1-7)
Antihypertensive Agents
Vasodilator Agents