<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/NCT01718197</url>
  </required_header>
  <id_info>
    <org_study_id>SARP-SF</org_study_id>
    <secondary_id>5U10HL109146-04</secondary_id>
    <nct_id>NCT01718197</nct_id>
  </id_info>
  <brief_title>Severe Asthma Research Program (SARP)- San Francisco Clinical Site</brief_title>
  <acronym>SARP</acronym>
  <official_title>Clinical and Molecular Phenotypes of Severe Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</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>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The mission of SARP is to improve the understanding of severe asthma through integrated study&#xD;
      of its clinical and biological features and to evaluate their changes over time. The ultimate&#xD;
      goal of these efforts is to promote better treatments for severe asthma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The mission of the SARP is to improve the understanding of severe asthma to develop better&#xD;
      treatments. The SARP will gain a better understanding of asthma and its endotypes, in&#xD;
      children and adults, by defining the disease at the molecular and cellular levels in the&#xD;
      context of the temporal phenotypic expression of the disease. To this end, the SARP&#xD;
      investigators will utilize both mechanistic and evoked phenotype approaches to: 1)&#xD;
      characterize developmental molecular, cellular and physiologic phenotypes in children and&#xD;
      adults with mild to severe asthma, and 2) to further elucidate the evolving pathobiology and&#xD;
      pathogenesis of severe asthma and its sub-phenotypes and 3) compare these features over time.&#xD;
&#xD;
      This approach involves a shared longitudinal protocol conducted across all participating&#xD;
      centers which includes common information on all SARP participants. Additionally, the SARP-SF&#xD;
      has identified mechanistic research questions to be included in the shared longitudinal&#xD;
      protocol. This will be explored through additional sample collections of sputum and fluids&#xD;
      and biopsied tissue collected by bronchoscopy. Together, these longitudinal and mechanistic&#xD;
      approaches will enable prediction of phenotype stability/fluctuation and pharmacologic&#xD;
      responses and identification of novel, disease-modifying targets for treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2012</start_date>
  <completion_date type="Actual">March 1, 2021</completion_date>
  <primary_completion_date type="Actual">February 18, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Lung function decline</measure>
    <time_frame>Enrollment, 1 year, 2 years, 3 years</time_frame>
    <description>Changes in lung function parameters over time.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Exacerbation frequency</measure>
    <time_frame>Monthly for 3 years</time_frame>
    <description>Number of oral corticosteroid requiring exacerbations of asthma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory cellular markers</measure>
    <time_frame>Enrollment, 1 year, 2 years, 3 years</time_frame>
    <description>Changes in inflammatory cellular markers in sputum, exhaled breath, and blood.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">151</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Mild-to-Moderate Asthma</arm_group_label>
    <description>Those with mild-to-moderate persistent asthma as defined by the NAEPP EPR-3 guidelines.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Severe Asthma</arm_group_label>
    <description>Major Criteria: (1 required)&#xD;
Treatment with oral corticosteroids for at least 6 of the previous 12 months&#xD;
Treatment with high-dose inhaled corticosteroids (ICS) for at least 10 of the previous 12 months&#xD;
Minor Criteria: (2 required)&#xD;
Daily treatment with an asthma controller medication in addition to ICS, or&#xD;
Asthma symptoms requiring short-acting bronchodilator use on a daily or near daily basis, or&#xD;
Persistent airway obstruction with baseline FEV1 &lt;80% predicted, or&#xD;
≥ 1 urgent visits for asthma in the previous 12 months, or&#xD;
≥ 3 systemic corticosteroid bursts in the previous 12 months, or&#xD;
Prompt deterioration with a reduction in oral or inhaled corticosteroid dose, or&#xD;
A near-fatal asthma event (i.e., intubation) in the past</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Those without asthma or other chronic lung disease.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood: CBC/Diff, Total IgE, Serum, Plasma, DNA, RNA Urine EBC Sputum: Supernatant, Cell&#xD;
      Pellet Bronchoscopy: BAL, Bronchial Brushings, Bronchial Biopsy&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        A diverse sample of subjects with asthma is needed to gain better understanding of asthma&#xD;
        and its endotypes. SARP will therefore enroll subjects 6 years and older with a physician&#xD;
        diagnosis of asthma. The target recruitment goal for each center is 75% adults (age 18 and&#xD;
        older) and 25% children age 6-17 years. Within the pediatric age group, an attempt will be&#xD;
        made to enroll equal numbers of children 6-11 and 12-17 years of age. Similarly, an attempt&#xD;
        will be made to enroll at least 50% females and 30% minorities.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  FEV1 bronchodilator reversibility ≥12% or airway hyperresponsiveness reflected by a&#xD;
             methacholine PC20 ≤16 mg/mL&#xD;
&#xD;
          -  An exception will be made for enrollees whose FEV1 is &lt; 50% predicted (&lt;70% in&#xD;
             children aged 6 to 17 years), precluding methacholine challenge testing. If&#xD;
             bronchodilator reversibility is &lt;12% in these participants, a diagnosis of asthma&#xD;
             acceptable to the investigator is sufficient for inclusion in SARP.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy during the characterization phase,&#xD;
&#xD;
          -  Current smoking,&#xD;
&#xD;
          -  Smoking history &gt; 10 pack years if ≥30 years of age, or smoking history &gt; 5 pack years&#xD;
             if &lt;30 years of age,&#xD;
&#xD;
          -  Other chronic pulmonary disorders associated with asthma-like symptoms, including (but&#xD;
             not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic&#xD;
             bronchitis, vocal cord dysfunction (that is the sole cause of respiratory symptoms and&#xD;
             at the PI's discretion), severe scoliosis or chest wall deformities that affect lung&#xD;
             function, or congenital disorders of the lungs or airways,&#xD;
&#xD;
          -  History of premature birth before 35 weeks gestation,&#xD;
&#xD;
          -  Unwillingness to receive an intramuscular triamcinolone acetonide injection&#xD;
&#xD;
          -  Evidence that the participant or family may be unreliable or poorly adherent to their&#xD;
             asthma treatment or study procedures,&#xD;
&#xD;
          -  Planning to relocate from the clinical center area before study completion,&#xD;
&#xD;
          -  Any other criteria that place the subject at unnecessary risk according to the&#xD;
             judgment of the Principal Investigator and/or attending physician(s) of record, or&#xD;
&#xD;
          -  Currently participating in an investigational drug trial.&#xD;
&#xD;
        Healthy Controls:&#xD;
&#xD;
        Inclusion criteria: Healthy subjects between the age of 18y and 65y. At least 3 of the 7&#xD;
        subjects per center should be aged 35y or older.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  History of chronic diseases that affect the lungs.&#xD;
&#xD;
          -  A history suggestive of allergic rhinitis, eczema or chronic sinusitis.&#xD;
&#xD;
          -  An improvement in FEV1 of more than 12% following 4 puffs of albuterol.&#xD;
&#xD;
          -  Smoking history &gt; 10 pack years if ≥30 years of age, or smoking history &gt; 5 pack years&#xD;
             if &lt;30 years of age, or any smoking within the past year.&#xD;
&#xD;
          -  Respiratory tract infection within the past 4 weeks.&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  History of premature birth (&lt;35 weeks).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John V Fahy, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <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_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.severeasthma.org/</url>
    <description>Severe Asthma Research Program Main Webpage</description>
  </link>
  <link>
    <url>http://acrc.ucsf.edu/</url>
    <description>UCSF Recruitment Website</description>
  </link>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>October 27, 2012</study_first_submitted>
  <study_first_submitted_qc>October 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 31, 2012</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Severe Asthma</keyword>
  <keyword>Bronchoscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_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/NCT01718197
org study id: SARP-SF
secondary id: 5U10HL109146-04
nct id: NCT01718197
lead sponsor: 
collaborator: 
has dmc: Yes
The mission of SARP is to improve the understanding of severe asthma through integrated study
      of its clinical and biological features and to evaluate their changes over time. The ultimate
      goal of these efforts is to promote better treatments for severe asthma.
The mission of the SARP is to improve the understanding of severe asthma to develop better
      treatments. The SARP will gain a better understanding of asthma and its endotypes, in
      children and adults, by defining the disease at the molecular and cellular levels in the
      context of the temporal phenotypic expression of the disease. To this end, the SARP
      investigators will utilize both mechanistic and evoked phenotype approaches to: 1)
      characterize developmental molecular, cellular and physiologic phenotypes in children and
      adults with mild to severe asthma, and 2) to further elucidate the evolving pathobiology and
      pathogenesis of severe asthma and its sub-phenotypes and 3) compare these features over time.

      This approach involves a shared longitudinal protocol conducted across all participating
      centers which includes common information on all SARP participants. Additionally, the SARP-SF
      has identified mechanistic research questions to be included in the shared longitudinal
      protocol. This will be explored through additional sample collections of sputum and fluids
      and biopsied tissue collected by bronchoscopy. Together, these longitudinal and mechanistic
      approaches will enable prediction of phenotype stability/fluctuation and pharmacologic
      responses and identification of novel, disease-modifying targets for treatment.
observational model: Cohort
time perspective: Prospective
measure: Lung function decline
time frame: Enrollment, 1 year, 2 years, 3 years
description: Changes in lung function parameters over time.
measure: Exacerbation frequency
time frame: Monthly for 3 years
description: Number of oral corticosteroid requiring exacerbations of asthma
measure: Inflammatory cellular markers
time frame: Enrollment, 1 year, 2 years, 3 years
description: Changes in inflammatory cellular markers in sputum, exhaled breath, and blood.
arm group label: Mild-to-Moderate Asthma
description: Those with mild-to-moderate persistent asthma as defined by the NAEPP EPR-3 guidelines.
arm group label: Severe Asthma
description: Major Criteria: (1 required)
Treatment with oral corticosteroids for at least 6 of the previous 12 months
Treatment with high-dose inhaled corticosteroids (ICS) for at least 10 of the previous 12 months
Minor Criteria: (2 required)
Daily treatment with an asthma controller medication in addition to ICS, or
Asthma symptoms requiring short-acting bronchodilator use on a daily or near daily basis, or
Persistent airway obstruction with baseline FEV1 <80% predicted, or
≥ 1 urgent visits for asthma in the previous 12 months, or
≥ 3 systemic corticosteroid bursts in the previous 12 months, or
Prompt deterioration with a reduction in oral or inhaled corticosteroid dose, or
A near-fatal asthma event (i.e., intubation) in the past
arm group label: Healthy Controls
description: Those without asthma or other chronic lung disease.
Blood: CBC/Diff, Total IgE, Serum, Plasma, DNA, RNA Urine EBC Sputum: Supernatant, Cell
      Pellet Bronchoscopy: BAL, Bronchial Brushings, Bronchial Biopsy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: John V Fahy, MD, MSc
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
url: http://www.severeasthma.org/
description: Severe Asthma Research Program Main Webpage
url: http://acrc.ucsf.edu/
description: UCSF Recruitment Website
responsible party type: Sponsor
mesh term: Asthma