<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/NCT03295734</url>
  </required_header>
  <id_info>
    <nct_id>NCT03295734</nct_id>
  </id_info>
  <brief_title>ACES - ACE Inhibitors Combined With Exercise for Seniors With Hypertension</brief_title>
  <acronym>ACES</acronym>
  <official_title>ACES - ACE Inhibitors Combined With Exercise for Seniors With Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Translational Research Institute for Metabolism and Diabetes, Advent Health Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Alabama at Birmingham</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 purpose of this project is to conduct a randomized, controlled trial (RCT) to determine&#xD;
      if choice of antihypertensive medication influences changes in functional status and other&#xD;
      cardiovascular risk factors among older persons with hypertension when combined with physical&#xD;
      exercise.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this project is to conduct a randomized, controlled trial (RCT) to determine&#xD;
      if choice of antihypertensive medication influences changes in functional status and other&#xD;
      cardiovascular risk factors among older persons with hypertension. Functional status,&#xD;
      determined by measures of physical performance, is an important predictor of cardiovascular&#xD;
      outcomes in older adults. Seniors with compromised function experience more CV events, have a&#xD;
      higher risk of undergoing cardiac surgery and higher risk of CVD-related death than&#xD;
      higher-functioning peers. Seniors with hypertension experience accelerated declines in&#xD;
      function, and presently physical exercise is the primary strategy for preventing this&#xD;
      decline. However, functional responses to exercise are highly variable and appear to be&#xD;
      influenced by the type of antihypertensive medication(s) utilized to control blood pressure.&#xD;
      Preliminary evidence suggests that, compared to other first-line antihypertensive agents,&#xD;
      angiotensin converting enzyme (ACE) inhibitors enhance exercise-derived improvements in&#xD;
      functional status among hypertensive seniors. This RCT will test this hypothesis. Sedentary&#xD;
      men and women &gt; 60 years of age with functional limitations and hypertension will be&#xD;
      recruited from two sites to participate in a longitudinal intervention study. Participants&#xD;
      will be randomly assigned to one of three first-line antihypertensive agents: (1) the ACE&#xD;
      inhibitor perindopril, (2) AT1 receptor antagonist losartan, or (3) the thiazide diuretic&#xD;
      hydrochlorothiazide. Note: Participants with a documented history of hypersensitivity to ACE&#xD;
      inhibitors will be randomized 1:1 to one of the two other study drugs. All participants will&#xD;
      also participate in a structured aerobic exercise intervention. The primary aim is to&#xD;
      determine if, compared to losartan and HCTZ, perindopril improves self-paced gait speed. The&#xD;
      secondary aim is to determine the relative effect of perindopril on a) exercise capacity, b)&#xD;
      body mass and composition, and c) circulating indices of cardiovascular risk. This study is&#xD;
      expected to differentiate beneficial effects of three FDA-approved antihypertensive&#xD;
      medications on an emerging cardiovascular risk factor in a clinically-relevant population.&#xD;
      Thus the study has important implications for expeditiously influencing clinical practice&#xD;
      guidelines in the prescription of antihypertensive drugs to millions of Americans.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 29, 2018</start_date>
  <completion_date type="Anticipated">May 2024</completion_date>
  <primary_completion_date type="Anticipated">May 2024</primary_completion_date>
  <phase>Phase 2</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gait speed</measure>
    <time_frame>32 weeks</time_frame>
    <description>Self-paced gait speed over 4m distance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Six minute walk test</measure>
    <time_frame>32 weeks</time_frame>
    <description>maximal distance covered over six minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition</measure>
    <time_frame>32 weeks</time_frame>
    <description>% body fat/lean mass collected via dual x-ray absorptiometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating indices of cardiovascular risk</measure>
    <time_frame>32 weeks</time_frame>
    <description>TNF-α, IL-6, VCAM-1, E-selectin; oxidized LDL; myeloperoxidase</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">213</enrollment>
  <condition>Hypertension</condition>
  <condition>Aging</condition>
  <condition>Sedentary Lifestyle</condition>
  <arm_group>
    <arm_group_label>Perindopril</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>4 mg qd titrated to 8 mg qd perindopril + aerobic exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Losartan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>50 mg qd titrated to 100 mg qd losartan + aerobic exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCTZ</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>12.5 mg qd titrated to 25 mg qd HCTZ + aerobic exercise</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Aerobic exercise</intervention_name>
    <description>Twice weekly centered based aerobic exercise + 3/week home-based walking</description>
    <arm_group_label>HCTZ</arm_group_label>
    <arm_group_label>Losartan</arm_group_label>
    <arm_group_label>Perindopril</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perindopril</intervention_name>
    <description>4 mg qd titrated to 8 mg qd perindopril</description>
    <arm_group_label>Perindopril</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Losartan</intervention_name>
    <description>50 mg qd titrated to 100 qd losartan</description>
    <arm_group_label>Losartan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HCTZ</intervention_name>
    <description>12.5 mg qd titrated to 25 qd HCTZ</description>
    <arm_group_label>HCTZ</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 60 years and older&#xD;
&#xD;
          -  Hypertension - untreated (SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg) or treated&#xD;
&#xD;
          -  &gt; 290 seconds needed to complete long-distance corridor walk test&#xD;
&#xD;
          -  Sedentary lifestyle, defined as &lt;150 min/wk of moderate physical activity&#xD;
&#xD;
          -  Willingness to participate in all study procedures, including allowing study team to&#xD;
             communicate with primary care physician regarding changes in antihypertensive&#xD;
             treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BP &gt; 140/90, despite the use of three or more anti-hypertensive drugs&#xD;
&#xD;
          -  SBP &gt; 180 mm Hg or DBP &gt; 110 mm Hg&#xD;
&#xD;
          -  Chronic kidney disease&#xD;
&#xD;
          -  Serum creatinine &gt;2.5 mg/dL in men or &gt;2.0 mg/dL in women&#xD;
&#xD;
          -  Serum potassium outside normal reference range&#xD;
&#xD;
          -  Urinary protein &gt; 1 on dipstick&#xD;
&#xD;
          -  Abnormal liver enzymes (AST, ALT, or alkaline phosphatase &gt; 2.5 times the upper limit&#xD;
             of normal)&#xD;
&#xD;
          -  Severe cardiac disease, including NYHA Class III or IV congestive heart failure,&#xD;
             clinically significant aortic stenosis, history of cardiac arrest, use of a cardiac&#xD;
             defibrillator, or uncontrolled angina&#xD;
&#xD;
          -  Acute myocardial infarction identified by ECG&#xD;
&#xD;
          -  Significant cognitive impairment, defined as a known diagnosis of dementia or a&#xD;
             Mini-Mental State Examination exam score &lt; 24;&#xD;
&#xD;
          -  Simultaneous participation in another intervention trial&#xD;
&#xD;
          -  Known hypersensitivity to ACE inhibitors (exclusion only to perindopril arm; will be&#xD;
             randomized among other two interventions)&#xD;
&#xD;
          -  Any other condition that would preclude participating based upon judgement of PI or&#xD;
             study clinician team&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Buford, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bret Goodpaster, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Translational Research Institute, Advent Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas Buford, PhD</last_name>
    <phone>2059963008</phone>
    <email>twbuford@uabmc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>UAB Center for Exercise Medicine</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Liliana Baptista, PhD</last_name>
      <email>lbaptista@uabmc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Translational Research Institute</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Susann Nagel</last_name>
      <email>Susann.Buller@AdventHealth.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 21, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>April 28, 2023</last_update_submitted>
  <last_update_submitted_qc>April 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Thomas W. Buford</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</mesh_term>
    <mesh_term>Perindopril</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03295734
nct id: NCT03295734
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this project is to conduct a randomized, controlled trial (RCT) to determine
      if choice of antihypertensive medication influences changes in functional status and other
      cardiovascular risk factors among older persons with hypertension when combined with physical
      exercise.
The purpose of this project is to conduct a randomized, controlled trial (RCT) to determine
      if choice of antihypertensive medication influences changes in functional status and other
      cardiovascular risk factors among older persons with hypertension. Functional status,
      determined by measures of physical performance, is an important predictor of cardiovascular
      outcomes in older adults. Seniors with compromised function experience more CV events, have a
      higher risk of undergoing cardiac surgery and higher risk of CVD-related death than
      higher-functioning peers. Seniors with hypertension experience accelerated declines in
      function, and presently physical exercise is the primary strategy for preventing this
      decline. However, functional responses to exercise are highly variable and appear to be
      influenced by the type of antihypertensive medication(s) utilized to control blood pressure.
      Preliminary evidence suggests that, compared to other first-line antihypertensive agents,
      angiotensin converting enzyme (ACE) inhibitors enhance exercise-derived improvements in
      functional status among hypertensive seniors. This RCT will test this hypothesis. Sedentary
      men and women > 60 years of age with functional limitations and hypertension will be
      recruited from two sites to participate in a longitudinal intervention study. Participants
      will be randomly assigned to one of three first-line antihypertensive agents: (1) the ACE
      inhibitor perindopril, (2) AT1 receptor antagonist losartan, or (3) the thiazide diuretic
      hydrochlorothiazide. Note: Participants with a documented history of hypersensitivity to ACE
      inhibitors will be randomized 1:1 to one of the two other study drugs. All participants will
      also participate in a structured aerobic exercise intervention. The primary aim is to
      determine if, compared to losartan and HCTZ, perindopril improves self-paced gait speed. The
      secondary aim is to determine the relative effect of perindopril on a) exercise capacity, b)
      body mass and composition, and c) circulating indices of cardiovascular risk. This study is
      expected to differentiate beneficial effects of three FDA-approved antihypertensive
      medications on an emerging cardiovascular risk factor in a clinically-relevant population.
      Thus the study has important implications for expeditiously influencing clinical practice
      guidelines in the prescription of antihypertensive drugs to millions of Americans.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Gait speed
time frame: 32 weeks
description: Self-paced gait speed over 4m distance
measure: Six minute walk test
time frame: 32 weeks
description: maximal distance covered over six minutes
measure: Body composition
time frame: 32 weeks
description: % body fat/lean mass collected via dual x-ray absorptiometry
measure: Circulating indices of cardiovascular risk
time frame: 32 weeks
description: TNF-α, IL-6, VCAM-1, E-selectin; oxidized LDL; myeloperoxidase
arm group label: Perindopril
arm group type: Active Comparator
description: 4 mg qd titrated to 8 mg qd perindopril + aerobic exercise
arm group label: Losartan
arm group type: Active Comparator
description: 50 mg qd titrated to 100 mg qd losartan + aerobic exercise
arm group label: HCTZ
arm group type: Active Comparator
description: 12.5 mg qd titrated to 25 mg qd HCTZ + aerobic exercise
intervention type: Behavioral
intervention name: Aerobic exercise
description: Twice weekly centered based aerobic exercise + 3/week home-based walking
arm group label: HCTZ
arm group label: Losartan
arm group label: Perindopril
intervention type: Drug
intervention name: Perindopril
description: 4 mg qd titrated to 8 mg qd perindopril
arm group label: Perindopril
intervention type: Drug
intervention name: Losartan
description: 50 mg qd titrated to 100 qd losartan
arm group label: Losartan
intervention type: Drug
intervention name: HCTZ
description: 12.5 mg qd titrated to 25 qd HCTZ
arm group label: HCTZ
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Buford, PhD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
last name: Bret Goodpaster, PhD
role: Principal Investigator
affiliation: Translational Research Institute, Advent Health
last name: Thomas Buford, PhD
phone: 2059963008
email: twbuford@uabmc.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Thomas W. Buford
investigator title: Associate Professor
mesh term: Hypertension
mesh term: Losartan
mesh term: Perindopril
sharing ipd: No