<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/NCT01684930</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00031918</org_study_id>
    <secondary_id>1R21HL111972-01</secondary_id>
    <nct_id>NCT01684930</nct_id>
  </id_info>
  <brief_title>Nitrites, Exercise, and Peripheral Arterial Disease</brief_title>
  <acronym>NO-PAD</acronym>
  <official_title>Increased Plasma Nitrite, Tissue Oxygenation and Functional Changes in PAD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The hypothesis of this proposal is that in subjects with PAD, regular consumption of a high&#xD;
      nitrate supplement which raises plasma nitrite, in conjunction with 12 weeks of supervised&#xD;
      exercise training at the limb ischemic threshold (SET) will produce a greater clinical&#xD;
      benefit (increases in COT and PWT) than placebo plus supervised exercise at the limb ischemic&#xD;
      threshold (PET).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</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>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption)</measure>
    <time_frame>Baseline and 16 Weeks</time_frame>
    <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change In Time To Exhaustion</measure>
    <time_frame>Baseline and 16 weeks</time_frame>
    <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Functional Ability</measure>
    <time_frame>Baseline and 16 Weeks</time_frame>
    <description>Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change In Claudication Onset Time</measure>
    <time_frame>Baseline and 16 weeks</time_frame>
    <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change In Vascular Function (BAFMD)</measure>
    <time_frame>Baseline and 16 weeks</time_frame>
    <description>Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Angiogenesis</measure>
    <time_frame>Baseline and 16 weeks</time_frame>
    <description>Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Peripheral Arterial Disease</condition>
  <arm_group>
    <arm_group_label>BR Juice (Beet-It Stamina Shot) and Exercise Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BR Juice Placebo and Exercise Training</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training</intervention_name>
    <description>The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
    <arm_group_label>BR Juice (Beet-It Stamina Shot) and Exercise Training</arm_group_label>
    <other_name>James White Drinks</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training</intervention_name>
    <description>The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
    <arm_group_label>BR Juice Placebo and Exercise Training</arm_group_label>
    <other_name>James White Drinks</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Peripheral Arterial Disease (ABI of less than 0.9)&#xD;
&#xD;
          -  Intermittent Claudication for 3 or more months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals with known alcohol or drug abuse problems&#xD;
&#xD;
          -  Individuals who have suffered a heart attack or stroke, or have changes on a resting&#xD;
             ECG, in the last 3 months&#xD;
&#xD;
          -  Those classified as American Heart Association Class D&#xD;
&#xD;
          -  Gangrene, impending limb loss or osteomyelitis&#xD;
&#xD;
          -  Lower extremity vascular surgery, angioplasty or lumbar sympathectomy within 3 months&#xD;
             of enrollment&#xD;
&#xD;
          -  Severe peripheral neuropathy&#xD;
&#xD;
          -  Any condition other than PAD that limits walking&#xD;
&#xD;
          -  Chest pain during treadmill exercise which appears before the onset of claudication,&#xD;
             or &gt;3mm ST depression during exercise&#xD;
&#xD;
          -  Subjects taking nitrates or nitroglycerin products&#xD;
&#xD;
          -  Must not be taking protein pump inhibitor medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason Allen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke Diet &amp; Fitness Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://cardiology.medicine.duke.edu/research/clinical-research/frederick-r-cobb-non-invasive-vascular-research-laboratory</url>
    <description>Frederick R. Cobb Non-Invasive Vascular Research Laboratory</description>
  </link>
  <link>
    <url>http://www.dukehealth.org/clinicaltrials/20120705125024398</url>
    <description>Duke Clinical Trials Listing</description>
  </link>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <results_first_submitted>November 25, 2015</results_first_submitted>
  <results_first_submitted_qc>November 25, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 1, 2016</results_first_posted>
  <last_update_submitted>August 26, 2017</last_update_submitted>
  <last_update_submitted_qc>August 26, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Jason Allen, Ph.D.</investigator_full_name>
    <investigator_title>Assistant Professor Doctor of Physical Therapy Program &amp; Division of Cardiovascular Medicine</investigator_title>
  </responsible_party>
  <keyword>Cardiovascular Diseases</keyword>
  <keyword>Vascular Diseases</keyword>
  <keyword>Arterial Occlusive Diseases</keyword>
  <keyword>Exercise</keyword>
  <keyword>Functional Capacity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Peripheral Arterial Disease</mesh_term>
    <mesh_term>Peripheral Vascular Diseases</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>10,817 patients were screened, 898 potential study candidates were identified, and 32 subjects signed consent and were enrolled from June 2012 through July 2014. Of the 32 subjects who signed consent, 5 subjects were screen failures and 1 withdrew consent. 26 subjects were randomized and 22 subjects completed all study testing.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
          <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
        </group>
        <group group_id="P2">
          <title>BR Juice Placebo and Exercise Training</title>
          <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
          <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
        </group>
        <group group_id="B2">
          <title>BR Juice Placebo and Exercise Training</title>
          <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="26"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.25" spread="8.9"/>
                    <measurement group_id="B2" value="71.85" spread="7.9"/>
                    <measurement group_id="B3" value="67.88" spread="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption)</title>
        <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.</description>
        <time_frame>Baseline and 16 Weeks</time_frame>
        <population>All participants who completed study.</population>
        <group_list>
          <group group_id="O1">
            <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
          </group>
          <group group_id="O2">
            <title>BR Juice Placebo and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption)</title>
          <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.</description>
          <population>All participants who completed study.</population>
          <units>ml/kg/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.48" spread="2.69"/>
                    <measurement group_id="O2" value="0.23" spread="2.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change In Time To Exhaustion</title>
        <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.</description>
        <time_frame>Baseline and 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
          </group>
          <group group_id="O2">
            <title>BR Juice Placebo and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
          </group>
        </group_list>
        <measure>
          <title>Change In Time To Exhaustion</title>
          <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="289.56" spread="175.44"/>
                    <measurement group_id="O2" value="254.92" spread="210.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Functional Ability</title>
        <description>Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.</description>
        <time_frame>Baseline and 16 Weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
          </group>
          <group group_id="O2">
            <title>BR Juice Placebo and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Functional Ability</title>
          <description>Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.</description>
          <units>feet</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="172.89" spread="166.05"/>
                    <measurement group_id="O2" value="95" spread="173.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change In Claudication Onset Time</title>
        <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.</description>
        <time_frame>Baseline and 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
          </group>
          <group group_id="O2">
            <title>BR Juice Placebo and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
          </group>
        </group_list>
        <measure>
          <title>Change In Claudication Onset Time</title>
          <description>Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.</description>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="199.22" spread="143.47"/>
                    <measurement group_id="O2" value="48.58" spread="198.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change In Vascular Function (BAFMD)</title>
        <description>Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .</description>
        <time_frame>Baseline and 16 weeks</time_frame>
        <population>participants with analyzable data</population>
        <group_list>
          <group group_id="O1">
            <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
          </group>
          <group group_id="O2">
            <title>BR Juice Placebo and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
          </group>
        </group_list>
        <measure>
          <title>Change In Vascular Function (BAFMD)</title>
          <description>Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .</description>
          <population>participants with analyzable data</population>
          <units>% dilation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.14" spread="3.02"/>
                    <measurement group_id="O2" value="-0.19" spread="1.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Angiogenesis</title>
        <description>Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups</description>
        <time_frame>Baseline and 16 weeks</time_frame>
        <population>Participants who had a gastrocnemius muscle biopsy with enough tissue to analyze.</population>
        <group_list>
          <group group_id="O1">
            <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
          </group>
          <group group_id="O2">
            <title>BR Juice Placebo and Exercise Training</title>
            <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Angiogenesis</title>
          <description>Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups</description>
          <population>Participants who had a gastrocnemius muscle biopsy with enough tissue to analyze.</population>
          <units>capillaries per fibrer</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.38" spread="0.54"/>
                    <measurement group_id="O2" value="0.26" spread="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>BR Juice (Beet-It Stamina Shot) and Exercise Training</title>
          <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Beetroot Juice (Beet-It Stamina Shot) &amp; Supervised Exercise Training: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.</description>
        </group>
        <group group_id="E2">
          <title>BR Juice Placebo and Exercise Training</title>
          <description>Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 &amp; 2) and at the end of the trial (between Visits 3 &amp; 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 &amp; 3) to when the subject has not consumed the beverage (Visits 1 &amp; 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 &amp; 3 and for all supervised exercise training visits during the 12 week intervention.&#xD;
Placebo Comparator Beverage (Beet-It Stamina Shot) &amp; Exercise Training: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>hypotensive episode with exercise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The largest limitation to the study was the evolving knowledge on conversion rates of oral inorganic nitrate to nitrite. We found a good deal of unexpected inter and intra-subject variation in conversion rates.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Jason D. Allen, PhD</name_or_title>
      <organization>Victoria University</organization>
      <phone>61 3 9919 4264</phone>
      <email>jason.allen@vu.edu.au</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01684930
org study id: Pro00031918
secondary id: 1R21HL111972-01
nct id: NCT01684930
lead sponsor: 
collaborator: 
has dmc: No
The hypothesis of this proposal is that in subjects with PAD, regular consumption of a high
      nitrate supplement which raises plasma nitrite, in conjunction with 12 weeks of supervised
      exercise training at the limb ischemic threshold (SET) will produce a greater clinical
      benefit (increases in COT and PWT) than placebo plus supervised exercise at the limb ischemic
      threshold (PET).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Change in Exercise Capacity: VO2peak (Maximal Oxygen Consumption)
time frame: Baseline and 16 Weeks
description: Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of peak oxygen consumption, claudication onset time and peak walking time.
measure: Change In Time To Exhaustion
time frame: Baseline and 16 weeks
description: Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of total time to exhaustion.
measure: Change in Functional Ability
time frame: Baseline and 16 Weeks
description: Six-Minute Walk test. This test simple and practical assessment of functional capacity. The test measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes. The test is self-paced and assesses the submaximal level of functional capacity. The subjects choose their own intensity and are allowed to stop and rest if necessary during the test.
measure: Change In Claudication Onset Time
time frame: Baseline and 16 weeks
description: Exercise capacity will be assessed using a maximal cardiopulmonary exercise (CPX) test with expired gas analysis, for determination of claudication onset time.
measure: Change In Vascular Function (BAFMD)
time frame: Baseline and 16 weeks
description: Vascular Function is measured as Brachial artery flow-mediated dilation (BAFMD). BAFMD is a measure of change in artery diameter after a stimulus .
measure: Change in Angiogenesis
time frame: Baseline and 16 weeks
description: Gastrocnemious muscle biopsy will be performed to measure the number of capillaries per fibre as a marker of change in angiogenesis between groups
arm group label: BR Juice (Beet-It Stamina Shot) and Exercise Training
arm group type: Experimental
description: Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of beetroot juice and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.
arm group label: BR Juice Placebo and Exercise Training
arm group type: Placebo Comparator
description: Subjects consume 70 ml of Beetroot Juice (Beet-It Stamina Shot; Placebo) to assess acute effects of beverage supplementation at the start (between Testing Visits 1 & 2) and at the end of the trial (between Visits 3 & 4). It also allows for comparisons of the combination of placebo beverage and chronic training effects (between Visits 2 & 3) to when the subject has not consumed the beverage (Visits 1 & 4). All subjects will consume Beet-It Stamina Shot (Placebo) 3 hours prior to all beverage tolerance visits, Testing Visits 2 & 3 and for all supervised exercise training visits during the 12 week intervention.
intervention type: Drug
intervention name: Beetroot Juice (Beet-It Stamina Shot) & Supervised Exercise Training
description: The beverage is high in inorganic nitrate and bottled and supplied by James White Drinks. This supplement will be used in conjunction with supervised exercise training.
arm group label: BR Juice (Beet-It Stamina Shot) and Exercise Training
other name: James White Drinks
intervention type: Other
intervention name: Placebo Comparator Beverage (Beet-It Stamina Shot) & Exercise Training
description: The beverage is identical in look and taste to Beet-It Stamina Shot but with active ingredient removed. It is also bottled and supplied by James White Drinks. This placebo supplement will be used in conjunction with supervised exercise training.
arm group label: BR Juice Placebo and Exercise Training
other name: James White Drinks
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Jason Allen, PhD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
url: http://cardiology.medicine.duke.edu/research/clinical-research/frederick-r-cobb-non-invasive-vascular-research-laboratory
description: Frederick R. Cobb Non-Invasive Vascular Research Laboratory
url: http://www.dukehealth.org/clinicaltrials/20120705125024398
description: Duke Clinical Trials Listing
responsible party type: Principal Investigator
investigator affiliation: Duke University
investigator full name: Jason Allen, Ph.D.
investigator title: Assistant Professor Doctor of Physical Therapy Program & Division of Cardiovascular Medicine
mesh term: Peripheral Arterial Disease
mesh term: Peripheral Vascular Diseases
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The largest limitation to the study was the evolving knowledge on conversion rates of oral inorganic nitrate to nitrite. We found a good deal of unexpected inter and intra-subject variation in conversion rates.
point of contact: 