<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/NCT01719042</url>
  </required_header>
  <id_info>
    <org_study_id>187-2012</org_study_id>
    <nct_id>NCT01719042</nct_id>
  </id_info>
  <brief_title>Improving Tolerance of Treatment of Pulmonary MAC Infections</brief_title>
  <acronym>ITT-MAC</acronym>
  <official_title>Improving Tolerance of Treatment of Pulmonary Mycobacterium Avium Complex Infections</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to improve tolerance of treatment of pulmonary Mycobacterium&#xD;
      avium Complex disease via the use of therapeutic drug monitoring and the addition of&#xD;
      anti-nausea medication or dietary supplements to the patients' daily drug regimen. The aims&#xD;
      of this study are to use (1) Zofran® (Ondansetron 8mg), an anti-nausea medication or (2) a&#xD;
      dietary supplement to decrease medication related gastrointestinal side effects of&#xD;
      medications used to treat Mycobacterium avium Complex.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As part of this study, investigators will review medical records to be sure that the patient&#xD;
      meets the required criteria and is healthy enough to take part in this study.&#xD;
&#xD;
      The study will consist of five separate visits to the Clinical research Center at the&#xD;
      University of Florida and each visit will last anywhere from 6-8 hours. Patients will be&#xD;
      given a diary of questionnaires where they will record when they take their medication and&#xD;
      any side effects they might have. Patients will also have Electrocardiograms (ECGs) to make&#xD;
      sure they are healthy enough to be a participant in the study and to measure the effects of&#xD;
      their medication on their heart. During this study, patients will continue treatment of their&#xD;
      Mycobacterium avium Complex infections. Patients will be observed taking their medication on&#xD;
      each of the five separate days. On each of these days patients will have blood drawn at 2 and&#xD;
      6 hours after their drugs are taken in order to measure drug levels in their blood. We will&#xD;
      also use this blood to measure levels of proteins and hormones and to make sure the&#xD;
      medications are not affecting the patient's heart. The patient will fill out several&#xD;
      questionnaires and do a dietary assessment online. Investigators will assess the patient's&#xD;
      body make-up using a device called the Bod Pod. The patient will also be assigned to one of&#xD;
      two treatment groups: (1) Ondansetron 8mg (Zofran®, GlaxoSmithKline, Research Triangle Park,&#xD;
      NC) every morning before breakfast versus (2) a dietary supplement prior to taking daily&#xD;
      medication. The patient will be assigned to the first treatment group for a period of two&#xD;
      weeks. On the third study visit investigators will switch the patient to the second group.&#xD;
&#xD;
      Although the incidence of tuberculosis has decreased in the United States over the last few&#xD;
      decades, the incidence of chronic pulmonary infections with nontuberculous mycobacteria (NTM)&#xD;
      appears to be increasing. Unfortunately, a common problem in the management of these&#xD;
      infections is the inability of elderly patients to tolerate the currently recommended&#xD;
      multidrug regimen of (1) azithromycin or clarithromycin, (2) rifampin or rifabutin, and (3)&#xD;
      ethambutol. The most frequent adverse reactions of MAC treatment are gastrointestinal (GI),&#xD;
      most commonly associated with the macrolides and rifampin. Although macrolide toxicity is&#xD;
      generally dose-related, the role of routine monitoring of drug concentrations and subsequent&#xD;
      dose adjustment has not been studied. The role of anti-emetics or dietary supplements to&#xD;
      mitigate these symptoms is also not defined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No recruitment was achievable&#xD;
  </why_stopped>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Gastroparesis Cardinal Symptom Index Score</measure>
    <time_frame>Change from baseline at the end of nine weeks</time_frame>
    <description>A survey instrument used to assess the severity of patient-reported gastrointestinal symptoms in clinical trials</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Leptin</measure>
    <time_frame>Baseline</time_frame>
    <description>Leptin is a natural hormone produced by your body's fat cells and acts as a signal which tells your brain you are no longer hungry</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in QTc on Electrocardiogram greater than 500 milliseconds</measure>
    <time_frame>Change from baseline at the end of nine weeks</time_frame>
    <description>To determine if the drug-drug interaction of azithromycin and Zofran (ondansetron) causes significant prolongation of the corrected QT (QTc) interval in this population of older female patients</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Mycobacterium Avium Complex</condition>
  <condition>Adverse Effects</condition>
  <arm_group>
    <arm_group_label>Zofran (8mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participant will take Zofran (8mg) once per day before taking their antibiotic regimen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ensure</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subject will drink a can of Ensure before taking their antibiotic regimen</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zofran (8mg)</intervention_name>
    <description>Subject will take 8mg of Zofran before taking antibiotic regimen and will record symptoms in a diary just before taking medication and two hours after taking medication every day for two weeks</description>
    <arm_group_label>Zofran (8mg)</arm_group_label>
    <other_name>Ondansetron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Ensure</intervention_name>
    <description>Subject will drink one cam of Ensure before taking antibiotic regimen and will record symptoms in a diary just before taking medication and two hours after taking medication every day for two weeks</description>
    <arm_group_label>Ensure</arm_group_label>
    <other_name>Ensure Plus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Physician diagnosis of Mycobacterium avium Complex with nodular bronchiectasis&#xD;
&#xD;
          -  On daily treatment for Mycobacterium avium Complex consisting of 250mg of&#xD;
             Azithromycin, 600mg of Rifampin, and 15mg/kg of Ethambutol&#xD;
&#xD;
          -  Experiencing gastrointestinal symptoms due to their multi-drug treatment regimen&#xD;
&#xD;
          -  Has access to the internet&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Currently smokes cigarettes&#xD;
&#xD;
          -  Persons with disseminated Mycobacterium avium Complex infections&#xD;
&#xD;
          -  Persons with a known and diagnosed immunosuppressive disorder (i.e. cancer, HIV)&#xD;
&#xD;
          -  Persons with physician diagnosed Irritable Bowel Syndrome, Crohn's Disease, or&#xD;
             Ulcerative Colitis&#xD;
&#xD;
          -  Persons with moderate to severe kidney or liver dysfunction&#xD;
&#xD;
          -  Persons who are co-colonized with an NTM aside from Mycobacterium avium Complex&#xD;
&#xD;
          -  Persons who initially present with a prolonged QT interval (defined as greater 500&#xD;
             milliseconds) on any baseline ECG&#xD;
&#xD;
          -  Previous adverse reaction or allergy to Zofran (Ondansetron)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin P Fennelly, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>April 2013</verification_date>
  <study_first_submitted>October 22, 2012</study_first_submitted>
  <study_first_submitted_qc>October 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>April 2, 2013</last_update_submitted>
  <last_update_submitted_qc>April 2, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 4, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycobacterium Infections</mesh_term>
    <mesh_term>Mycobacterium avium-intracellulare Infection</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ondansetron</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01719042
org study id: 187-2012
nct id: NCT01719042
lead sponsor: 
has dmc: No
The purpose of this study is to improve tolerance of treatment of pulmonary Mycobacterium
      avium Complex disease via the use of therapeutic drug monitoring and the addition of
      anti-nausea medication or dietary supplements to the patients' daily drug regimen. The aims
      of this study are to use (1) Zofran® (Ondansetron 8mg), an anti-nausea medication or (2) a
      dietary supplement to decrease medication related gastrointestinal side effects of
      medications used to treat Mycobacterium avium Complex.
As part of this study, investigators will review medical records to be sure that the patient
      meets the required criteria and is healthy enough to take part in this study.

      The study will consist of five separate visits to the Clinical research Center at the
      University of Florida and each visit will last anywhere from 6-8 hours. Patients will be
      given a diary of questionnaires where they will record when they take their medication and
      any side effects they might have. Patients will also have Electrocardiograms (ECGs) to make
      sure they are healthy enough to be a participant in the study and to measure the effects of
      their medication on their heart. During this study, patients will continue treatment of their
      Mycobacterium avium Complex infections. Patients will be observed taking their medication on
      each of the five separate days. On each of these days patients will have blood drawn at 2 and
      6 hours after their drugs are taken in order to measure drug levels in their blood. We will
      also use this blood to measure levels of proteins and hormones and to make sure the
      medications are not affecting the patient's heart. The patient will fill out several
      questionnaires and do a dietary assessment online. Investigators will assess the patient's
      body make-up using a device called the Bod Pod. The patient will also be assigned to one of
      two treatment groups: (1) Ondansetron 8mg (Zofran®, GlaxoSmithKline, Research Triangle Park,
      NC) every morning before breakfast versus (2) a dietary supplement prior to taking daily
      medication. The patient will be assigned to the first treatment group for a period of two
      weeks. On the third study visit investigators will switch the patient to the second group.

      Although the incidence of tuberculosis has decreased in the United States over the last few
      decades, the incidence of chronic pulmonary infections with nontuberculous mycobacteria (NTM)
      appears to be increasing. Unfortunately, a common problem in the management of these
      infections is the inability of elderly patients to tolerate the currently recommended
      multidrug regimen of (1) azithromycin or clarithromycin, (2) rifampin or rifabutin, and (3)
      ethambutol. The most frequent adverse reactions of MAC treatment are gastrointestinal (GI),
      most commonly associated with the macrolides and rifampin. Although macrolide toxicity is
      generally dose-related, the role of routine monitoring of drug concentrations and subsequent
      dose adjustment has not been studied. The role of anti-emetics or dietary supplements to
      mitigate these symptoms is also not defined.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Change in Gastroparesis Cardinal Symptom Index Score
time frame: Change from baseline at the end of nine weeks
description: A survey instrument used to assess the severity of patient-reported gastrointestinal symptoms in clinical trials
measure: Leptin
time frame: Baseline
description: Leptin is a natural hormone produced by your body's fat cells and acts as a signal which tells your brain you are no longer hungry
measure: Change in QTc on Electrocardiogram greater than 500 milliseconds
time frame: Change from baseline at the end of nine weeks
description: To determine if the drug-drug interaction of azithromycin and Zofran (ondansetron) causes significant prolongation of the corrected QT (QTc) interval in this population of older female patients
arm group label: Zofran (8mg)
arm group type: Active Comparator
description: Participant will take Zofran (8mg) once per day before taking their antibiotic regimen
arm group label: Ensure
arm group type: Active Comparator
description: Subject will drink a can of Ensure before taking their antibiotic regimen
intervention type: Drug
intervention name: Zofran (8mg)
description: Subject will take 8mg of Zofran before taking antibiotic regimen and will record symptoms in a diary just before taking medication and two hours after taking medication every day for two weeks
arm group label: Zofran (8mg)
other name: Ondansetron
intervention type: Dietary Supplement
intervention name: Ensure
description: Subject will drink one cam of Ensure before taking antibiotic regimen and will record symptoms in a diary just before taking medication and two hours after taking medication every day for two weeks
arm group label: Ensure
other name: Ensure Plus
criteria: 
gender: Female
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Kevin P Fennelly, MD, MPH
role: Principal Investigator
affiliation: University of Florida
country: United States
responsible party type: Sponsor
mesh term: Mycobacterium Infections
mesh term: Mycobacterium avium-intracellulare Infection
mesh term: Ondansetron