<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/NCT02230332</url>
  </required_header>
  <id_info>
    <org_study_id>AsthmaNet 009</org_study_id>
    <secondary_id>U10HL098115</secondary_id>
    <nct_id>NCT02230332</nct_id>
  </id_info>
  <brief_title>Alendronate to Prevent Loss of Bronchoprotection in Asthma</brief_title>
  <acronym>ALFA</acronym>
  <official_title>Proof of Concept Study of Alendronate for Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Milton S. Hershey Medical Center</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>Milton S. Hershey Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Beta-2-agonists are effective in reducing airway narrowing in asthma and protecting against&#xD;
      stimuli that produce bronchoconstriction. The combination of long-acting beta agonists (LABA)&#xD;
      and inhaled corticosteroids (ICS) has become the most commonly used asthma controller&#xD;
      medication class in the United States, but unfortunately, even when LABAs are added to ICS&#xD;
      and used regularly, 58-81% of patients with asthma fail to achieve total control. Regular use&#xD;
      of beta-agonists, both short and long-acting, reduces the ability of these agents to protect&#xD;
      against the airway narrowing that occurs in asthma in response to bronchoconstrictor stimuli.&#xD;
      We refer to this reduced effect as loss of bronchoprotection. In this proof of concept trial&#xD;
      we aim to determine if alendronate, which diminishes beta-2 adrenergic receptor&#xD;
      internalization, can reduce the loss of bronchoprotection that occurs with regular use of&#xD;
      LABAs, even when used in combination with ICS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Salmeterol Protected Methacholine Challenge PC20</measure>
    <time_frame>8 weeks after randomization</time_frame>
    <description>Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density</measure>
    <time_frame>8 weeks after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beta-2 Adrenergic Receptor Agonist-induced cAMP Production</measure>
    <time_frame>8 weeks after randomization</time_frame>
    <description>Peripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol)</measure>
    <time_frame>8 weeks after randomization</time_frame>
    <description>Salivary Alpha Amylase (sAA) levels from saliva samples obtained through passive drooling, before and 1 hour after Salmeterol administration. The outcome is expressed as the ratio of the Post-Salmeterol to the Pre-Salmeterol sAA levels.</description>
  </other_outcome>
  <other_outcome>
    <measure>Asthma Control Test (ACT)</measure>
    <time_frame>8 weeks after randomization</time_frame>
    <description>Asthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.</description>
  </other_outcome>
  <other_outcome>
    <measure>Fractional Exhaled Nitrix Oxide</measure>
    <time_frame>8 weeks after randomization</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">78</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Alendronate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alendronate in 10mg capsules taken once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo capsule taken once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alendronate</intervention_name>
    <arm_group_label>Alendronate</arm_group_label>
    <other_name>Fasomax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical history consistent with moderate asthma for &gt;1 year&#xD;
&#xD;
          -  Asthma is controlled with ICS, with an FP dose ≤ 1000mcg/day and &gt;100mcg/day (or&#xD;
             equivalent)&#xD;
&#xD;
          -  Able to perform reproducible spirometry according to ATS criteria&#xD;
&#xD;
          -  Baseline FEV1 ≥ 50% of predicted and ≥1L.&#xD;
&#xD;
          -  If FEV1 &lt;80%, a minimum 12% increase in FEV1 post-bronchodilator or a MCh PC20 ≤ 8&#xD;
             mg/mL&#xD;
&#xD;
          -  If FEV1 ≥80%, a MCh PC20 ≤ 8 mg/mL&#xD;
&#xD;
          -  Salmeterol protected MCh ≤ 16 mg/mL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled asthma, as suggested by an ACT score &lt;18 while on high-dose ICS (FP daily&#xD;
             dose &gt;500mcg or equivalent)&#xD;
&#xD;
          -  Non-ICS controller medication or LABA use within 4 weeks of study entry.&#xD;
&#xD;
          -  Contraindications to use of bisphosphonates: history of intolerance to&#xD;
             bisphosphonates, history of esophageal ulcers, history of hematemesis, uncontrolled&#xD;
             gastro-esophageal reflux disease, inability to stay erect for 30 minutes after oral&#xD;
             drug, history of osteonecrosis of the jaw, dental extraction or root canal in prior 8&#xD;
             weeks, or anticipated during the study&#xD;
&#xD;
          -  Calculated GFR of less than 35 mL/min&#xD;
&#xD;
          -  History of smoking (cigarettes, cigars, pipes, marijuana or any other substances)&#xD;
             within the past 1 year, or &gt; 10 pack-years total if ≥ 18 years of age&#xD;
&#xD;
          -  Systemic corticosteroid treatment for any condition within 4 weeks of enrollment at&#xD;
             Visit 1, history of significant asthma exacerbation requiring systemic corticosteroids&#xD;
             within 4 weeks of Visit 1 or more than five courses of systemic corticosteroids in the&#xD;
             past year, history of a life-threatening asthma exacerbation requiring intubation,&#xD;
             mechanical ventilation, or resulting in a hypoxic seizure within the last 2 years&#xD;
&#xD;
          -  History of a respiratory tract infection within 4 weeks of Visit 1&#xD;
&#xD;
          -  Receiving hyposensitization therapy other than an established maintenance regimen&#xD;
             defined as a continuous regimen for ≥ 3 months prior to enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juan Carlos Cardet, MD</last_name>
    <role>Study Director</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arizona College of Medicine</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California - San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Jewish Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham &amp; Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53972</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://asthmanetresearch.org/</url>
    <description>AsthmaNet home page</description>
  </link>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <results_first_submitted>October 2, 2017</results_first_submitted>
  <results_first_submitted_qc>November 9, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 14, 2017</results_first_posted>
  <last_update_submitted>December 13, 2017</last_update_submitted>
  <last_update_submitted_qc>December 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Milton S. Hershey Medical Center</investigator_affiliation>
    <investigator_full_name>dave mauger</investigator_full_name>
    <investigator_title>Professor of Public Health Sciences</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alendronate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Eligible participants were recruited from the community between January 2015 and May 2016 at 9 U.S. sites from the NHLBI AsthmaNet research network.</recruitment_details>
      <pre_assignment_details>Participants with persistent asthma were first treated with fluticasone propionate 250mcg twice daily for 2 weeks during the run-in. Most of the participants who were not randomized did not meet the Salmeterol Protected Methacholine Challenge inclusion criterion.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Alendronate</title>
          <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo capsule taken once daily&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="34"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Alendronate</title>
          <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo capsule taken once daily&#xD;
Placebo</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="38"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="78"/>
          </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="38.3" spread="13.1"/>
                    <measurement group_id="B2" value="39.3" spread="12.3"/>
                    <measurement group_id="B3" value="38.8" spread="12.6"/>
                  </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="20"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian/Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic or Latio</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Asthma Control Test score</title>
          <description>Asthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="21" lower_limit="18" upper_limit="23"/>
                    <measurement group_id="B2" value="21" lower_limit="19" upper_limit="23"/>
                    <measurement group_id="B3" value="21" lower_limit="19" upper_limit="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>FEV1 - percent of predicted</title>
          <units>percent of predicted</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="81.3" spread="14.9"/>
                    <measurement group_id="B2" value="83.1" spread="14.0"/>
                    <measurement group_id="B3" value="82.2" spread="14.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Salmeterol Protected Methcholine PC20</title>
          <description>During the challenge, the patient inhales methacholine aerosols in increasing concentrations. Spirometry is performed before and after each methacholine dose, and the results are reported as a percent decrease in FEV1 from baseline for each increasing dose of methacholine. A positive reaction to methacholine is a 20% fall in FEV1, and the provocative concentration that causes a positive reaction (the PC20) is used to indicate the level of airway hyperresponsiveness. Smaller numbers indicate greater airway hyperresponsiveness.</description>
          <units>mg/ml</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5.4" spread="0.8"/>
                    <measurement group_id="B2" value="3.7" spread="1"/>
                    <measurement group_id="B3" value="4.5" spread="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Salmeterol Protected Methacholine Challenge PC20</title>
        <description>Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.</description>
        <time_frame>8 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alendronate</title>
            <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo capsule taken once daily&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Salmeterol Protected Methacholine Challenge PC20</title>
          <description>Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.</description>
          <units>mg/ml on log base 2 scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.8" lower_limit="1.1" upper_limit="2.5"/>
                    <measurement group_id="O2" value="1.7" lower_limit="1.1" upper_limit="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density</title>
        <time_frame>8 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alendronate</title>
            <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo capsule taken once daily&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density</title>
          <units>number of receptors per cell</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1680" lower_limit="1359" upper_limit="2076"/>
                    <measurement group_id="O2" value="1863" lower_limit="1473" upper_limit="2358"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Beta-2 Adrenergic Receptor Agonist-induced cAMP Production</title>
        <description>Peripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.</description>
        <time_frame>8 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alendronate</title>
            <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo capsule taken once daily&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Beta-2 Adrenergic Receptor Agonist-induced cAMP Production</title>
          <description>Peripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.</description>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9" lower_limit="4.7" upper_limit="7.5"/>
                    <measurement group_id="O2" value="5.9" lower_limit="4.9" upper_limit="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol)</title>
        <description>Salivary Alpha Amylase (sAA) levels from saliva samples obtained through passive drooling, before and 1 hour after Salmeterol administration. The outcome is expressed as the ratio of the Post-Salmeterol to the Pre-Salmeterol sAA levels.</description>
        <time_frame>8 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alendronate</title>
            <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo capsule taken once daily&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol)</title>
          <description>Salivary Alpha Amylase (sAA) levels from saliva samples obtained through passive drooling, before and 1 hour after Salmeterol administration. The outcome is expressed as the ratio of the Post-Salmeterol to the Pre-Salmeterol sAA levels.</description>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" lower_limit="1.4" upper_limit="1.9"/>
                    <measurement group_id="O2" value="1.6" lower_limit="1.3" upper_limit="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Asthma Control Test (ACT)</title>
        <description>Asthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.</description>
        <time_frame>8 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alendronate</title>
            <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo capsule taken once daily&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Asthma Control Test (ACT)</title>
          <description>Asthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2" lower_limit="21.2" upper_limit="23.2"/>
                    <measurement group_id="O2" value="22.2" lower_limit="21.4" upper_limit="23.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Fractional Exhaled Nitrix Oxide</title>
        <time_frame>8 weeks after randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Alendronate</title>
            <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo capsule taken once daily&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Fractional Exhaled Nitrix Oxide</title>
          <units>parts per billion</units>
          <param>Geometric Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="34"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.8" lower_limit="12.9" upper_limit="21.9"/>
                    <measurement group_id="O2" value="15.4" lower_limit="11.7" upper_limit="20.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Alendronate</title>
          <description>Alendronate in 10mg capsules taken once daily&#xD;
Alendronate</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo capsule taken once daily&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>ICD-9</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>GI Bleed</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Viral Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>ICD-9</default_vocab>
        <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="9" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Esophageal reflux</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Heartburn</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="38"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Nausea alone</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>thrush</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute nasopharyngitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Acute sinusitis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="38"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Acue Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>asthma exacerbation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="38"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="40"/>
              </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>David Mauger, PhD</name_or_title>
      <organization>Penn State University Dept of Public Health Sciences</organization>
      <phone>717.531.3584</phone>
      <email>dmauger@psu.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/NCT02230332
org study id: AsthmaNet 009
secondary id: U10HL098115
nct id: NCT02230332
lead sponsor: 
collaborator: 
has dmc: Yes
Beta-2-agonists are effective in reducing airway narrowing in asthma and protecting against
      stimuli that produce bronchoconstriction. The combination of long-acting beta agonists (LABA)
      and inhaled corticosteroids (ICS) has become the most commonly used asthma controller
      medication class in the United States, but unfortunately, even when LABAs are added to ICS
      and used regularly, 58-81% of patients with asthma fail to achieve total control. Regular use
      of beta-agonists, both short and long-acting, reduces the ability of these agents to protect
      against the airway narrowing that occurs in asthma in response to bronchoconstrictor stimuli.
      We refer to this reduced effect as loss of bronchoprotection. In this proof of concept trial
      we aim to determine if alendronate, which diminishes beta-2 adrenergic receptor
      internalization, can reduce the loss of bronchoprotection that occurs with regular use of
      LABAs, even when used in combination with ICS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Salmeterol Protected Methacholine Challenge PC20
time frame: 8 weeks after randomization
description: Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.
measure: Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density
time frame: 8 weeks after randomization
measure: Beta-2 Adrenergic Receptor Agonist-induced cAMP Production
time frame: 8 weeks after randomization
description: Peripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.
measure: Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol)
time frame: 8 weeks after randomization
description: Salivary Alpha Amylase (sAA) levels from saliva samples obtained through passive drooling, before and 1 hour after Salmeterol administration. The outcome is expressed as the ratio of the Post-Salmeterol to the Pre-Salmeterol sAA levels.
measure: Asthma Control Test (ACT)
time frame: 8 weeks after randomization
description: Asthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.
measure: Fractional Exhaled Nitrix Oxide
time frame: 8 weeks after randomization
arm group label: Alendronate
arm group type: Experimental
description: Alendronate in 10mg capsules taken once daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo capsule taken once daily
intervention type: Drug
intervention name: Alendronate
arm group label: Alendronate
other name: Fasomax
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Juan Carlos Cardet, MD
role: Study Director
affiliation: Brigham and Women's Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://asthmanetresearch.org/
description: AsthmaNet home page
responsible party type: Principal Investigator
investigator affiliation: Milton S. Hershey Medical Center
investigator full name: dave mauger
investigator title: Professor of Public Health Sciences
mesh term: Asthma
mesh term: Alendronate
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 