<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/NCT04501926</url>
  </required_header>
  <id_info>
    <org_study_id>PI-29/17</org_study_id>
    <nct_id>NCT04501926</nct_id>
  </id_info>
  <brief_title>Genomics and Metagenomics of Asthma Severity</brief_title>
  <acronym>GEMAS</acronym>
  <official_title>Genomics and Metagenomics of Asthma Severity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maria Pino-Yanes</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of La Laguna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Spanish Ministry of Science, Innovation, and Universities</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Consorcio Centro de Investigación Biomédica en Red (CIBER)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital of the Nuestra Señora de Candelaria</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario de Canarias</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital General de La Palma</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario Donostia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Doctor Jose Molina Orosa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of La Laguna</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of&#xD;
      genomics, the microbiome, and the interaction between them in the development of asthma&#xD;
      exacerbations in European patients with asthma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow&#xD;
      obstruction and a bronchial hyperreactivity in response to a variety of stimuli. In most&#xD;
      patients, the onset of asthma symptoms may be controlled. However, many of them may manifest&#xD;
      asthma attacks or crises of breathing called exacerbations, which occur with breathing&#xD;
      problems, wheezing, coughing or tightness of chest, and may threaten their life. Such&#xD;
      exacerbations are caused by a combination of environmental and genetic factors. However,&#xD;
      since studies so far have been limited, a reduced number of genes associated with the&#xD;
      predisposition to these complications have been identified. In addition, some studies have&#xD;
      used next-generation DNA sequencing techniques to characterize the microbiome (i.e.,&#xD;
      microbial community) of the airways, finding changes related to asthma. The main hypothesis&#xD;
      of the Genomics and Metagenomics of Asthma Severity (GEMAS) study is that exacerbations of&#xD;
      asthma are caused by a combination of the intrinsic genetic factors of the individual,&#xD;
      changes in the respiratory microbiome and the interaction between both factors. The&#xD;
      objectives of this project are: 1) to identify genetic variants that are associated with&#xD;
      asthma exacerbations; 2) to examine the changes occurring in the microbial communities of the&#xD;
      oral cavity and respiratory tract in individuals with exacerbations; 3) to analyze the&#xD;
      association of the host genetic variants and the microbiome changes related to exacerbations.&#xD;
&#xD;
      A total of 300 Spanish subjects with asthma with and without a history of asthma&#xD;
      exacerbations in the past 12 months will be recruited. Saliva, nasal and pharyngeal samples&#xD;
      will be collected to study the oral cavity and the upper respiratory tract microbiome through&#xD;
      next-generation sequencing technologies. Sequencing of the 16S ribosomal RNA (16S rRNA) gene&#xD;
      will allow to characterize the bacterial diversity and abundance, as well as to infer the&#xD;
      functionality of the microbiome in each sample. These parameters will be used to establish&#xD;
      correlations between the microbiome and the presence of asthma exacerbations. Finally, the&#xD;
      association between the genetic variation associated with exacerbations in genomic studies&#xD;
      and the measurements of abundance, diversity and functions related to exacerbations will be&#xD;
      jointly examined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Severe asthma exacerbations</measure>
    <time_frame>1 year</time_frame>
    <description>Defined by one of the following events because of asthma during the past year, the past 6 months, and the past week: oral corticosteroids use, emergency room visit, and/or hospitalizations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Asthma control</measure>
    <time_frame>1 week</time_frame>
    <description>Asthma control questionnaire (ACQ) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asthma severity</measure>
    <time_frame>1 year</time_frame>
    <description>Category of severity defined by treatment step according to GINA 2020 at recruitment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function measurement: forced expiratory volume in the first second (FEV1)</measure>
    <time_frame>3 months</time_frame>
    <description>Baseline and post-bronchodilator measurements of the forced expiratory volume in the first second (FEV1) measured in liters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function measurement: forced vital capacity (FVC)</measure>
    <time_frame>3 months</time_frame>
    <description>Baseline and post-bronchodilator measurements of the forced vital capacity (FVC) measured in liters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lung function measurement: FEV1/FVC ratio</measure>
    <time_frame>3 months</time_frame>
    <description>The ratio of FEV1/FVC measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atopy testing</measure>
    <time_frame>1 year</time_frame>
    <description>Atopy status evaluated by skin prick tests and/or specific immunoglobulin E (IgE) levels assessing the most common aeroallergens of each recruiting center</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Asthma</condition>
  <condition>Asthma Attack</condition>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Asthma patients who did not report asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cases</arm_group_label>
    <description>Asthma patients that reported asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples are drown in EDTA tubes and PAXGene tubes for human DNA and RNA extraction,&#xD;
      respectively. For the human microbiome study, saliva samples and nasal and pharyngeal swaps&#xD;
      are collected.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients are recruited from the allergy and/or pulmonary medicine units from hospitals&#xD;
        located in the Canary Islands, Spain (Hospital Universitario de Canarias, Hospital&#xD;
        Universitario Nuestra Señora de Candelaria, Hospital General de La Palma, and Hospital&#xD;
        Doctor Jose Molina Orosa), and in the division of pediatric respiratory medicine of&#xD;
        Hospital Universitario Donostia in the Basque Country, Spain.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female aged older or equal than 8 years and younger or equal than 85 years&#xD;
&#xD;
          -  Physician diagnosis of asthma according to the Global Initiative for Asthma (GINA)&#xD;
             guidelines&#xD;
&#xD;
          -  Treated on GINA step 1-5&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  One or more grandparents of non-European origin&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Coexistence of other chronic pulmonary disorders including cystic fibrosis, chronic&#xD;
             obstructive pulmonary disease (emphysema or chronic bronchitis), or congenital&#xD;
             disorders of the lungs or airways&#xD;
&#xD;
          -  Known family relatedness (first or second degree) with another participant already&#xD;
             included in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Maria Pino-Yanes, Ph.D.</last_name>
    <phone>+34 922 316 502</phone>
    <phone_ext>6343</phone_ext>
    <email>mdelpino@ull.edu.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Fabian Lorenzo-Diaz, Ph.D.</last_name>
    <phone>+34 922 316 502</phone>
    <phone_ext>8350</phone_ext>
    <email>florenzo@ull.edu.es</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of La Laguna</name>
      <address>
        <city>San Cristobal de la Laguna</city>
        <state>Santa Cruz De Tenerife</state>
        <zip>38200</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Doctor Jose Molina Orosa</name>
      <address>
        <city>Arrecife</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Berta Roman-Bernal, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital General de La Palma</name>
      <address>
        <city>Breña Alta</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jose M Hernandez-Perez, MD, Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Canarias</name>
      <address>
        <city>San Cristobal de la Laguna</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ruperto Gonzalez-Perez, MD, Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Donostia</name>
      <address>
        <city>San Sebastián</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olaia Sardon, MD, Ph.D.</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Nuestra Señora de Candelaria</name>
      <address>
        <city>Santa Cruz De Tenerife</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jose M Hernandez-Perez, MD, Ph.D.</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>May 16, 2022</last_update_submitted>
  <last_update_submitted_qc>May 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of La Laguna</investigator_affiliation>
    <investigator_full_name>Maria Pino-Yanes</investigator_full_name>
    <investigator_title>Ramon y Cajal Fellow and Lecturer</investigator_title>
  </responsible_party>
  <keyword>Genome-Wide Association Study</keyword>
  <keyword>Microbiome, Human</keyword>
  <keyword>Asthma</keyword>
  <keyword>Epigenomics</keyword>
  <keyword>Transcriptomics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04501926
org study id: PI-29/17
nct id: NCT04501926
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The Genomics and Metagenomics of Asthma Severity (GEMAS) study aims to assess the role of
      genomics, the microbiome, and the interaction between them in the development of asthma
      exacerbations in European patients with asthma.
Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow
      obstruction and a bronchial hyperreactivity in response to a variety of stimuli. In most
      patients, the onset of asthma symptoms may be controlled. However, many of them may manifest
      asthma attacks or crises of breathing called exacerbations, which occur with breathing
      problems, wheezing, coughing or tightness of chest, and may threaten their life. Such
      exacerbations are caused by a combination of environmental and genetic factors. However,
      since studies so far have been limited, a reduced number of genes associated with the
      predisposition to these complications have been identified. In addition, some studies have
      used next-generation DNA sequencing techniques to characterize the microbiome (i.e.,
      microbial community) of the airways, finding changes related to asthma. The main hypothesis
      of the Genomics and Metagenomics of Asthma Severity (GEMAS) study is that exacerbations of
      asthma are caused by a combination of the intrinsic genetic factors of the individual,
      changes in the respiratory microbiome and the interaction between both factors. The
      objectives of this project are: 1) to identify genetic variants that are associated with
      asthma exacerbations; 2) to examine the changes occurring in the microbial communities of the
      oral cavity and respiratory tract in individuals with exacerbations; 3) to analyze the
      association of the host genetic variants and the microbiome changes related to exacerbations.

      A total of 300 Spanish subjects with asthma with and without a history of asthma
      exacerbations in the past 12 months will be recruited. Saliva, nasal and pharyngeal samples
      will be collected to study the oral cavity and the upper respiratory tract microbiome through
      next-generation sequencing technologies. Sequencing of the 16S ribosomal RNA (16S rRNA) gene
      will allow to characterize the bacterial diversity and abundance, as well as to infer the
      functionality of the microbiome in each sample. These parameters will be used to establish
      correlations between the microbiome and the presence of asthma exacerbations. Finally, the
      association between the genetic variation associated with exacerbations in genomic studies
      and the measurements of abundance, diversity and functions related to exacerbations will be
      jointly examined.
observational model: Case-Control
time perspective: Retrospective
measure: Severe asthma exacerbations
time frame: 1 year
description: Defined by one of the following events because of asthma during the past year, the past 6 months, and the past week: oral corticosteroids use, emergency room visit, and/or hospitalizations
measure: Asthma control
time frame: 1 week
description: Asthma control questionnaire (ACQ) score
measure: Asthma severity
time frame: 1 year
description: Category of severity defined by treatment step according to GINA 2020 at recruitment
measure: Lung function measurement: forced expiratory volume in the first second (FEV1)
time frame: 3 months
description: Baseline and post-bronchodilator measurements of the forced expiratory volume in the first second (FEV1) measured in liters
measure: Lung function measurement: forced vital capacity (FVC)
time frame: 3 months
description: Baseline and post-bronchodilator measurements of the forced vital capacity (FVC) measured in liters
measure: Lung function measurement: FEV1/FVC ratio
time frame: 3 months
description: The ratio of FEV1/FVC measurements
measure: Atopy testing
time frame: 1 year
description: Atopy status evaluated by skin prick tests and/or specific immunoglobulin E (IgE) levels assessing the most common aeroallergens of each recruiting center
arm group label: Controls
description: Asthma patients who did not report asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.
arm group label: Cases
description: Asthma patients that reported asthma exacerbations in the 12 months prior recruitment, defined by one of the following events because of asthma: oral corticosteroids use, emergency room visits, and/or hospitalizations.
Blood samples are drown in EDTA tubes and PAXGene tubes for human DNA and RNA extraction,
      respectively. For the human microbiome study, saliva samples and nasal and pharyngeal swaps
      are collected.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 8 Years
maximum age: 85 Years
healthy volunteers: No
last name: Maria Pino-Yanes, Ph.D.
phone: +34 922 316 502
phone ext: 6343
email: mdelpino@ull.edu.es
last name: Fabian Lorenzo-Diaz, Ph.D.
phone: +34 922 316 502
phone ext: 8350
email: florenzo@ull.edu.es
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Spain
responsible party type: Sponsor-Investigator
investigator affiliation: University of La Laguna
investigator full name: Maria Pino-Yanes
investigator title: Ramon y Cajal Fellow and Lecturer
mesh term: Asthma
sharing ipd: No