<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/NCT01681836</url>
  </required_header>
  <id_info>
    <org_study_id>PRO11120134</org_study_id>
    <nct_id>NCT01681836</nct_id>
  </id_info>
  <brief_title>Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults</brief_title>
  <official_title>An Open-Label Study of Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gladwin, Mark, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will&#xD;
      result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited&#xD;
      toxicity in the doses proposed in healthy adult normal volunteers. We utilize a powerful in&#xD;
      vivo technique (pharmacokinetic testing) and are the first to design inorganic nitrate and&#xD;
      nitrite capsules for cardiovascular disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preclinical and clinical research over the last decade has revealed the important&#xD;
      vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure,&#xD;
      vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate&#xD;
      and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral&#xD;
      formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid&#xD;
      acting effects upon absorption, while the nitrate would continuously provide a slow formation&#xD;
      of nitrite over a prolonged period of time via the enterosalivary circulation pathway.&#xD;
&#xD;
      For this reason, development of an oral formulation of nitrate and nitrite salts is&#xD;
      attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the&#xD;
      nitrate would continuously provide a slow formation of nitrite over a prolonged period of&#xD;
      time via the enterosalivary circulation pathway. This study aims to establish the&#xD;
      pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric&#xD;
      oxide in vivo in healthy adult normal volunteers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak Plasma Nitrate Concentration Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
    <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak Plasma Nitrite Concentration Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
    <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
    <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Percentage Level of Methemoglobin Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
    <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change in Mean Arterial Pressure Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported</time_frame>
    <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change in Systolic Blood Pressure Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported</time_frame>
    <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported</time_frame>
    <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period</measure>
    <time_frame>measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose</time_frame>
    <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Platelet Activation at 6 Hours</measure>
    <time_frame>measured at 0 (baseline), 6 and 24 hours post-dose</time_frame>
    <description>at timepoint with greatest change from 0 (trough); &quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change in Heart Rate Over 24 Hour Study Period</measure>
    <time_frame>measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite</time_frame>
    <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Focus of Study of Healthy Adults</condition>
  <arm_group>
    <arm_group_label>Oral 15N-labeled sodium nitrate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral 15N-labeled sodium nitrite</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>15Nitrogen(15N)-labeled sodium nitrite</intervention_name>
    <description>15Nitrogen(15N)-labeled sodium nitrite 20 mg once</description>
    <arm_group_label>Oral 15N-labeled sodium nitrate</arm_group_label>
    <arm_group_label>Oral 15N-labeled sodium nitrite</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>15Nitrogen(15N)-labeled sodium nitrate</intervention_name>
    <description>15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once</description>
    <arm_group_label>Oral 15N-labeled sodium nitrate</arm_group_label>
    <arm_group_label>Oral 15N-labeled sodium nitrite</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-60 years&#xD;
&#xD;
          -  Systolic blood pressure ≤130 and diastolic blood pressure ≤85 mm Hg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Positive urine pregnancy test or breastfeeding&#xD;
&#xD;
          -  Concurrent use of medications affecting glucose or lipid metabolism&#xD;
&#xD;
          -  Recent addition or change in dosing of hormonal contraceptive medications (oral&#xD;
             contraceptive pill, intrauterine device, DepoProvera)&#xD;
&#xD;
          -  Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or&#xD;
             normotensive on a single agent&#xD;
&#xD;
          -  Current use of phosphodiesterase 5 inhibitors or organic nitrates&#xD;
&#xD;
          -  Not stable on treatments for the prior three months or not planning to remain on&#xD;
             current dose of medications for blood pressure, contraception, etc&#xD;
&#xD;
          -  Known chronic psychiatric or medical conditions including diabetes, liver or kidney&#xD;
             disease or obesity syndromes&#xD;
&#xD;
          -  Smoker&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kara S Hughan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark T Gladwin, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bret Goodpaster, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Montefiore Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 3, 2012</study_first_submitted>
  <study_first_submitted_qc>September 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2012</study_first_posted>
  <results_first_submitted>February 24, 2016</results_first_submitted>
  <results_first_submitted_qc>August 31, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 4, 2018</results_first_posted>
  <last_update_submitted>August 31, 2018</last_update_submitted>
  <last_update_submitted_qc>August 31, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Kara Hughan</investigator_full_name>
    <investigator_title>Instructor of Pediatrics</investigator_title>
  </responsible_party>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Healthy adult participants were recruited between October 2012 and October 2013.</recruitment_details>
      <pre_assignment_details>11 participants recruited; 11 screened; 0 excluded</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Oral 15N-labeled Sodium Nitrate, Then Sodium Nitrite</title>
          <description>Oral 15N-labeled sodium nitrate 1,000 mg once in first intervention period and oral 15N-labeled sodium nitrite 20 mg once in second intervention period (after washout period)</description>
        </group>
        <group group_id="P2">
          <title>Oral 15N-labeled Sodium Nitrite, Then Sodium Nitrate</title>
          <description>Oral 15N-labeled sodium nitrite 20 mg once in first intervention period and oral 15N-labeled sodium nitrate 1,000 mg once in second intervention period (after washout period)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period of 3-7 Days</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Second Intervention</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <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="0"/>
                <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>Entire Study Population</title>
          <description>Includes groups randomized to received oral 15N-labeled sodium nitrate first and sodium nitrite first.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.4" lower_limit="21" upper_limit="39"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Systolic blood pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="122" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diastolic blood pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75" spread="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean arterial pressure</title>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="91" spread="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Methemoglobin</title>
          <units>percentage level of methemoglobin</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.0" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Peak Plasma Nitrate Concentration Over 24 Hour Study Period</title>
        <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Plasma Nitrate Concentration Over 24 Hour Study Period</title>
          <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>microMolar (microM)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="769" spread="38"/>
                    <measurement group_id="O2" value="41" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Peak Plasma Nitrite Concentration Over 24 Hour Study Period</title>
        <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Plasma Nitrite Concentration Over 24 Hour Study Period</title>
          <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>microM</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.51" spread="0.1"/>
                    <measurement group_id="O2" value="5.5" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period</title>
        <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period</title>
          <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>microMolar</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" spread="NA">not detectable</measurement>
                    <measurement group_id="O2" value="1.04" spread="0.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Percentage Level of Methemoglobin Over 24 Hour Study Period</title>
        <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Percentage Level of Methemoglobin Over 24 Hour Study Period</title>
          <description>&quot;Post-doses&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>percentage level</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.24" spread="0.08"/>
                    <measurement group_id="O2" value="1.59" spread="0.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change in Mean Arterial Pressure Over 24 Hour Study Period</title>
        <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change in Mean Arterial Pressure Over 24 Hour Study Period</title>
          <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.9" spread="2.1"/>
                    <measurement group_id="O2" value="-10.4" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change in Systolic Blood Pressure Over 24 Hour Study Period</title>
        <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change in Systolic Blood Pressure Over 24 Hour Study Period</title>
          <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="2.9"/>
                    <measurement group_id="O2" value="-12.1" spread="10.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period</title>
        <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period</title>
          <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>mmHg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.3" spread="1.2"/>
                    <measurement group_id="O2" value="-8.1" spread="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period</title>
        <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose</time_frame>
        <population>maximal at 24 hours with nitrate treatment, not detectable with nitrite treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period</title>
          <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <population>maximal at 24 hours with nitrate treatment, not detectable with nitrite treatment</population>
          <units>nanoMolar</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.14" lower_limit="0" upper_limit="25.3"/>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">not detectable</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Platelet Activation at 6 Hours</title>
        <description>at timepoint with greatest change from 0 (trough); &quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry</description>
        <time_frame>measured at 0 (baseline), 6 and 24 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Platelet Activation at 6 Hours</title>
          <description>at timepoint with greatest change from 0 (trough); &quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry</description>
          <units>% of platelets that are activated</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.0" spread="1.7"/>
                    <measurement group_id="O2" value="8.3" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change in Heart Rate Over 24 Hour Study Period</title>
        <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
        <time_frame>measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral 15N-labeled Sodium Nitrate</title>
            <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
          </group>
          <group group_id="O2">
            <title>Oral 15N-labeled Sodium Nitrite</title>
            <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change in Heart Rate Over 24 Hour Study Period</title>
          <description>&quot;Post-dose&quot; refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period</description>
          <units>beats per minute</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6" spread="4.1"/>
                    <measurement group_id="O2" value="9" spread="4.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3-7 days after single dose of each drug</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Oral 15N-labeled Sodium Nitrate</title>
          <description>Oral 15N-labeled sodium nitrate 1,000 mg once in either first intervention period or second intervention period</description>
        </group>
        <group group_id="E2">
          <title>Oral 15N-labeled Sodium Nitrite</title>
          <description>Oral 15N-labeled sodium nitrite 20 mg once in either first intervention period or second intervention period</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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>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="9" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Stomach ache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Mean arterial pressure decrease &gt;20%</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of breath</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <point_of_contact>
      <name_or_title>Dr. Kara Hughan</name_or_title>
      <organization>University of Pittsburgh</organization>
      <phone>412-692-5170</phone>
      <email>kara.hughan@chp.edu</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/NCT01681836
org study id: PRO11120134
nct id: NCT01681836
lead sponsor: 
has dmc: No
This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will
      result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited
      toxicity in the doses proposed in healthy adult normal volunteers. We utilize a powerful in
      vivo technique (pharmacokinetic testing) and are the first to design inorganic nitrate and
      nitrite capsules for cardiovascular disease.
Preclinical and clinical research over the last decade has revealed the important
      vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure,
      vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate
      and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral
      formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid
      acting effects upon absorption, while the nitrate would continuously provide a slow formation
      of nitrite over a prolonged period of time via the enterosalivary circulation pathway.

      For this reason, development of an oral formulation of nitrate and nitrite salts is
      attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the
      nitrate would continuously provide a slow formation of nitrite over a prolonged period of
      time via the enterosalivary circulation pathway. This study aims to establish the
      pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric
      oxide in vivo in healthy adult normal volunteers.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: None (Open Label)
measure: Peak Plasma Nitrate Concentration Over 24 Hour Study Period
time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
description: "Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak Plasma Nitrite Concentration Over 24 Hour Study Period
time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
description: "Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak Red Blood Cell (RBC) Iron-nitrosyl Hemoglobin (NO-Hb) Concentrations Over 24 Hour Study Period
time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
description: "Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15Nitrogen(15N)-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak Percentage Level of Methemoglobin Over 24 Hour Study Period
time frame: measured at 0 (baseline), 0.5, 1, 2, 3, 6 and 24 hours post-doses
description: "Post-doses" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak Change in Mean Arterial Pressure Over 24 Hour Study Period
time frame: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
description: "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak Change in Systolic Blood Pressure Over 24 Hour Study Period
time frame: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours reported
description: "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak Change in Diastolic Blood Pressure Over 24 Hour Study Period
time frame: measured at 0 (baseline) then every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 0.75 hours reported
description: "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Peak 15Nitrogen Nitro-conjugated Linoleic Acid (cLA) Concentrations Over 24 Hour Study Period
time frame: measured at time 0 (trough), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose
description: "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
measure: Percent Platelet Activation at 6 Hours
time frame: measured at 0 (baseline), 6 and 24 hours post-dose
description: at timepoint with greatest change from 0 (trough); "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period; percentage of platelets that express 2 specific markers identifying activated platelets (CD41 and CD62-P) were quantified using flow cytometry
measure: Peak Change in Heart Rate Over 24 Hour Study Period
time frame: measured at 0 (baseline), every 15 minutes during the first 2 hours post-dose, then at 3, 6, and 24 hours post-dose, change at 1.5 hours for nitrate and 24 hours for nitrite
description: "Post-dose" refers to that subjects will receive a single dose of each study drug, oral 15N-labeled sodium nitrate and nitrite, in random order, separated by a 3-7 day washout period
arm group label: Oral 15N-labeled sodium nitrate
arm group type: Experimental
description: Oral sodium nitrate 1,000 mg once first, then washout followed by oral sodium nitrite 20 mg once
arm group label: Oral 15N-labeled sodium nitrite
arm group type: Experimental
description: Oral sodium nitrite 20 mg once first, then washout followed by oral sodium nitrate 1,000 mg once
intervention type: Drug
intervention name: 15Nitrogen(15N)-labeled sodium nitrite
description: 15Nitrogen(15N)-labeled sodium nitrite 20 mg once
arm group label: Oral 15N-labeled sodium nitrate
arm group label: Oral 15N-labeled sodium nitrite
intervention type: Drug
intervention name: 15Nitrogen(15N)-labeled sodium nitrate
description: 15Nitrogen(15N)-labeled sodium nitrate 1,000 mg once
arm group label: Oral 15N-labeled sodium nitrate
arm group label: Oral 15N-labeled sodium nitrite
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kara S Hughan, MD
role: Principal Investigator
affiliation: University of Pittsburgh
last name: Mark T Gladwin, MD
role: Study Director
affiliation: University of Pittsburgh
last name: Bret Goodpaster, PhD
role: Study Director
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Kara Hughan
investigator title: Instructor of Pediatrics
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 