<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03777215</url>
  </required_header>
  <id_info>
    <org_study_id>00009895</org_study_id>
    <nct_id>NCT03777215</nct_id>
  </id_info>
  <brief_title>Angiotensin-(1-7) and Energy Expenditure in Human Obesity</brief_title>
  <official_title>Angiotensin-(1-7) and Energy Expenditure in Human Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amy Arnold</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Milton S. Hershey Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to better define the role of the hormone angiotensin-(1-7) in&#xD;
      energy balance. We will test the overall hypothesis that angiotensin-(1-7) increases resting&#xD;
      energy expenditure and promotes markers of heat production (thermogenesis) in white adipose&#xD;
      tissue in human obesity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to produce&#xD;
      positive cardiovascular and metabolic effects in animal models. In this study, the&#xD;
      investigators will determine if angiotensin-(1-7) can increase resting energy expenditure and&#xD;
      promote white adipose tissue heat production (thermogenesis) in obese human subjects. The&#xD;
      investigators will perform a randomized, double-blind, two-arm parallel group study to&#xD;
      determine effects of acute intravenous angiotensin-(1-7) versus saline infusion on resting&#xD;
      energy expenditure measured by indirect calorimetry in obese human participants. In addition,&#xD;
      blood pressure and heart rate will be measured and blood samples obtained to measure for&#xD;
      changes in circulating renin-angiotensin system and metabolic hormones. Abdominal&#xD;
      subcutaneous white adipose biopsies will also be obtained from obese human participants&#xD;
      during acute angiotensin-(1-7) versus saline infusions to examine for changes in gene&#xD;
      expression for markers of thermogenesis. The findings from these studies will advance&#xD;
      understanding of hormonal mechanisms involved in the etiology of obesity, and provide new&#xD;
      insight into the potential for targeting angiotensin-(1-7) to improve energy balance in human&#xD;
      obesity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 26, 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Resting energy expenditure</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Uncoupling protein 1</measure>
    <time_frame>120 minutes</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in heart rate following angiotensin-(1-7) versus saline infusion</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Skin temperature</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in skin temperature following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Skin blood flow</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in skin blood flow following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Abdominal heat production</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Catecholamines</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Insulin</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Glucose</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Fatty acids</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Angiotensin II</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Angiotensin-(1-7)</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Renin</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma renin activity following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <other_outcome>
    <measure>Aldosterone</measure>
    <time_frame>120 minutes</time_frame>
    <description>Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Angiotensin-(1-7)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Angiotensin-(1-7)</intervention_name>
    <description>This is a biologically active beneficial hormone of the renin-angiotensin system.</description>
    <arm_group_label>Angiotensin-(1-7)</arm_group_label>
    <other_name>Angiotensin I/II (1-7) Acetate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Saline will be used as the placebo comparator.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>0.9% sodium chloride</other_name>
    <other_name>normal saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women of all races&#xD;
&#xD;
          -  Capable of giving informed consent&#xD;
&#xD;
          -  Age 18-60 years&#xD;
&#xD;
          -  Body mass index (BMI) between 30-40 kg/m2&#xD;
&#xD;
          -  Satisfactory history and physical exam&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age ≤ 17 or ≥ 61 years&#xD;
&#xD;
          -  Pregnant, nursing, or postmenopausal women&#xD;
&#xD;
          -  Decisional impairment&#xD;
&#xD;
          -  Prisoners&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Current smokers&#xD;
&#xD;
          -  Highly trained athletes&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Subjects with &gt;5% weight change in the past 3 months&#xD;
&#xD;
          -  Evidence of type I or type II diabetes (fasting glucose &gt; 126 mg/dL or use of&#xD;
             anti-diabetic medications)&#xD;
&#xD;
          -  History of serious cardiovascular disease other than hypertension (e.g. myocardial&#xD;
             infarction within 6 months, symptomatic coronary artery disease, presence of angina&#xD;
             pectoris, significant arrhythmia, congestive heart failure, deep vein thrombosis,&#xD;
             pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic&#xD;
             stenosis, hypertrophic cardiomyopathy) or cerebrovascular disease (e.g. cerebral&#xD;
             hemorrhage, stroke, transient Ischemic attack).&#xD;
&#xD;
          -  History or presence of immunological or hematological disorders&#xD;
&#xD;
          -  Impaired hepatic function (aspartate aminotransferase or alanine aminotransferase&#xD;
             levels &gt;2 times upper limit of normal range)&#xD;
&#xD;
          -  Impaired renal function (serum creatinine &gt;2.0 mg/dl)&#xD;
&#xD;
          -  Anemia&#xD;
&#xD;
          -  Treatment with anticoagulants (e.g. warfarin)&#xD;
&#xD;
          -  Treatment with chronic systemic glucocorticoid therapy (&gt;7 consecutive days in 1&#xD;
             month)&#xD;
&#xD;
          -  Treatment with medications influencing energy expenditure (e.g. psychostimulants)&#xD;
&#xD;
          -  Treatment with any investigational drug in the 1-month preceding the study&#xD;
&#xD;
          -  Inability to give, or withdraw, informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amy C Arnold, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pennsylvania State University College of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aimee C Cauffman, BSN</last_name>
    <phone>717-531-1617</phone>
    <email>acauffman@pennstatehealth.psu.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Penn State Milton S. Hershey Medical Center</name>
      <address>
        <city>Hershey</city>
        <state>Pennsylvania</state>
        <zip>17033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy C Arnold, PhD</last_name>
      <phone>717-531-3674</phone>
      <email>aarnold5@pennstatehealth.psu.edu</email>
    </contact>
    <investigator>
      <last_name>Urs A Leuenberger, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Faisal Aziz, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>John Radtka, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>David N Proctor, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cheryl Blaha, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Aimee Cauffman, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Milton S. Hershey Medical Center</investigator_affiliation>
    <investigator_full_name>Amy Arnold</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angiotensin I (1-7)</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual participant data will not be made available to other researchers.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03777215
org study id: 00009895
nct id: NCT03777215
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Resting energy expenditure
time frame: 120 minutes
description: Change in resting energy expenditure measured by indirect calorimetry at baseline and at end of angiotensin-(1-7) versus saline infusion.
measure: Uncoupling protein 1
time frame: 120 minutes
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.
measure: Blood pressure
time frame: 120 minutes
description: Change in arm and finger cuff blood pressure following angiotensin-(1-7) versus saline infusion
measure: Heart rate
time frame: 120 minutes
description: Change in heart rate following angiotensin-(1-7) versus saline infusion
measure: Skin temperature
time frame: 120 minutes
description: Change in skin temperature following angiotensin-(1-7) versus saline infusion
measure: Skin blood flow
time frame: 120 minutes
description: Change in skin blood flow following angiotensin-(1-7) versus saline infusion
measure: Abdominal heat production
time frame: 120 minutes
description: Change in abdominal heat production as measured by thermal imaging following angiotensin-(1-7) versus saline infusion
measure: Catecholamines
time frame: 120 minutes
description: Change in plasma catecholamines following angiotensin-(1-7) versus saline infusion
measure: Insulin
time frame: 120 minutes
description: Change in plasma insulin levels following angiotensin-(1-7) versus saline infusion
measure: Glucose
time frame: 120 minutes
description: Change in plasma glucose levels following angiotensin-(1-7) versus saline infusion
measure: Fatty acids
time frame: 120 minutes
description: Change in plasma free fatty acid levels following angiotensin-(1-7) versus saline infusion
measure: Angiotensin II
time frame: 120 minutes
description: Change in plasma angiotensin II levels following angiotensin-(1-7) versus saline infusion
measure: Angiotensin-(1-7)
time frame: 120 minutes
description: Change in plasma angiotensin-(1-7) levels following angiotensin-(1-7) versus saline infusion
measure: Renin
time frame: 120 minutes
description: Change in plasma renin activity following angiotensin-(1-7) versus saline infusion
measure: Aldosterone
time frame: 120 minutes
description: Change in plasma aldosterone levels following angiotensin-(1-7) versus saline infusion
arm group label: Angiotensin-(1-7)
arm group type: Experimental
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.
arm group label: Placebo
arm group type: Placebo Comparator
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: Angiotensin-(1-7)
description: This is a biologically active beneficial hormone of the renin-angiotensin system.
arm group label: Angiotensin-(1-7)
other name: Angiotensin I/II (1-7) Acetate
intervention type: Drug
intervention name: Saline
description: Saline will be used as the placebo comparator.
arm group label: Placebo
other name: 0.9% sodium chloride
other name: normal saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Amy C Arnold, PhD
role: Principal Investigator
affiliation: Pennsylvania State University College of Medicine
last name: Aimee C Cauffman, BSN
phone: 717-531-1617
email: acauffman@pennstatehealth.psu.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Milton S. Hershey Medical Center
investigator full name: Amy Arnold
investigator title: Assistant Professor
mesh term: Obesity
mesh term: Angiotensin I (1-7)
sharing ipd: No
ipd description: Individual participant data will not be made available to other researchers.