<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/NCT03278561</url>
  </required_header>
  <id_info>
    <org_study_id>GRANDMA</org_study_id>
    <nct_id>NCT03278561</nct_id>
  </id_info>
  <brief_title>General Risk Factors and Inflammatory Determinants in Older Patients With Asthma</brief_title>
  <acronym>GRANDMA</acronym>
  <official_title>General Risk Factors and Inflammatory Determinants in Older Patients With Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gerdien Tramper</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Franciscus Gasthuis</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>
      A cross-sectional study in asthma patients to determine if a late age of onset asthma (start&#xD;
      symptoms &gt;18 years old), is associated with more persistent airway/systemic inflammation,&#xD;
      worse asthma control, more co-morbidity, a different microbiome and poorer quality of life&#xD;
      despite the use of optimized asthma therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For ages, asthma has been considered a disease for children and young adults. However,&#xD;
      nowadays 30% of all asthma patients is over 50 years old. Asthma in the elderly is generally&#xD;
      more severe and approximately 50% of all deaths drom asthma occur in this age group. With&#xD;
      rapid aging of the global population, the burden of asthma in the elderly will further&#xD;
      increase.&#xD;
&#xD;
      Asthma is a heterogeneous disease and the question is whether asthma in the elderly can be&#xD;
      considered the same disease as asthma in children and young adults. The pathophysiology and&#xD;
      risk factors of asthma in the elderly are still not completely understood. Good&#xD;
      characterization of asthma in the elderly requires clinical phenotyping as well as a thorough&#xD;
      analysis of the underlying cellular and molecular mechanisms. It is hypothesized that in&#xD;
      older asthma patients, a late age of onset (start asthma symptoms &gt;18 years) is associated&#xD;
      with more persistent airway/systemic inflammation, worse asthma control, more co-morbidity&#xD;
      and poorer quality of life despite the use of optimized asthma therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 8, 2017</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">August 31, 2019</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Differences in number and activation status of inflammatory cells in sputum and blood</measure>
    <time_frame>1 month</time_frame>
    <description>To compare the differences in number and activation status of inflammatory cells in sputum and blood of different subgroups of asthmatics.)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Interleukin cell type 2 (ILC2) correlation and disease phenotype</measure>
    <time_frame>1 month</time_frame>
    <description>To find correlations between ILC2 numbers and characteristics and immunological and clinical disease phenotype. -</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hair cortisol</measure>
    <time_frame>1 month</time_frame>
    <description>Detection of cortisol levels in hair, to determine a possible method to check Inhaled corticosteroid (ICS) adherence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory profile</measure>
    <time_frame>1 month</time_frame>
    <description>To measure physiological factors (lung function, activity level) and relate them to inflammatory profile.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Selfmanagement / coping strategies</measure>
    <time_frame>1 month</time_frame>
    <description>To investigate the relationship between duration and onset of asthma and self-management/coping strategies of patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.</measure>
    <time_frame>1 month</time_frame>
    <description>The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Detection of different microbiome subgroups of asthmatics and compare with controls.</measure>
    <time_frame>1 month</time_frame>
    <description>Detection of microflora/microbiome pattern in sputum and faeces in different subgroups of asthmatics and compare with controls.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">90</enrollment>
  <condition>Asthma</condition>
  <condition>Late-Onset Asthma</condition>
  <condition>Childhood Asthma</condition>
  <arm_group>
    <arm_group_label>Early onset asthma</arm_group_label>
    <description>Sputum induction according to the European Respiratory Society (ERS) protocol. A blood sample of 100ml will be taken.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Late onset asthma</arm_group_label>
    <description>Sputum induction according to the ERS protocol. A blood sample of 100ml will be taken.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No pulmonary disease</arm_group_label>
    <description>Sputum induction according to the ERS protocol. A blood sample of 100ml will be taken.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sputum induction</intervention_name>
    <description>Sputum induction according to the ERS protocol</description>
    <arm_group_label>Early onset asthma</arm_group_label>
    <arm_group_label>Late onset asthma</arm_group_label>
    <arm_group_label>No pulmonary disease</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>A blood sample of 100ml will be taken.</description>
    <arm_group_label>Early onset asthma</arm_group_label>
    <arm_group_label>Late onset asthma</arm_group_label>
    <arm_group_label>No pulmonary disease</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      sputum, blood, NP swab, feces&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The aim is to enrol 30 patients with early onset asthma (age of onset &lt; 18 years) and 30&#xD;
        patients with late onset asthma (age of onset &gt; 18 years); all with a smoking history of &lt;&#xD;
        10 PY. Both groups consist of 15 older asthma patients (&gt; 50 years) and 15 younger asthma&#xD;
        patients (&lt; 50 years); per age group 15 healthy controls serve as comparison (no asthma).&#xD;
        Asthma diagnosis is based on presence of typical clinical symptoms, reversible airway&#xD;
        obstruction (+12% improvement in FEV1 after bronchodilator) or bronchial hyperreactivity&#xD;
        (PC20 &lt; 8 mg/ml) or a FeNO &gt; 50 ppb. All asthma patients have GINA step 4-5 medication&#xD;
        (high dose ICS/LABA) and are not adequately controlled (ACQ &gt; 0,75)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria Asthma patients:&#xD;
&#xD;
          -  Age between 18-80 years&#xD;
&#xD;
          -  Smoking history of &lt; 10 packyears (PY)&#xD;
&#xD;
          -  Willing and able to comply with the study protocol&#xD;
&#xD;
          -  Asthma diagnosis is based on presence of typical clinical symptoms, reversible airway&#xD;
             obstruction (+12% improvement in forced expiratory volume at one second (FEV1) after&#xD;
             bronchodilator) or bronchial hyperreactivity (PC20 &lt; 8 mg/ml) or a (fractional exhaled&#xD;
             nitric oxide) FeNO &gt; 50 ppb. - All asthma patients have (Global Initiative for Asthma&#xD;
             ) GINA step 4-5 medication (high dose ICS/LABA).&#xD;
&#xD;
          -  Asthma control questionaire (ACQ) &gt; 0,75&#xD;
&#xD;
          -  Written informed consent.&#xD;
&#xD;
        Inclusion Criteria Healthy controls:\Inclusion criteria healthy control:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age between 18-80 years.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking history of &gt; 10 PY&#xD;
&#xD;
          -  Age &lt; 18 years or &gt; 80 years&#xD;
&#xD;
          -  Not able to speak or write Dutch language.&#xD;
&#xD;
          -  Not able to perform lung function test/sputum induction&#xD;
&#xD;
          -  ACQ &lt; 0,75&#xD;
&#xD;
          -  Other diseases which could influence pulmonary function and/or the immune system such&#xD;
             as: o A possible infection of the upper- or lower respiratory tract 4 weeks prior to&#xD;
             the collection of materials;&#xD;
&#xD;
               -  Chronic obstructive pulmonary disorder (COPD) in the medical history;&#xD;
&#xD;
               -  Auto-immune diseases such as systemic lupus erythematosus (SLE), rheumatoid&#xD;
                  arthritis (RA), myasthenia gravis or Goodpasture's syndrome;&#xD;
&#xD;
               -  Malignancies;&#xD;
&#xD;
               -  Inherited or acquired immunodeficiency&#xD;
&#xD;
               -  Pregnancy;&#xD;
&#xD;
        Exclusion criteria healthy controls:&#xD;
&#xD;
          -  Asthma, as defined earlier (page 13);&#xD;
&#xD;
          -  An abnormal spirometry with a forced vital capacity (FVC) or FEV1 below the 80% of the&#xD;
             predicted value&#xD;
&#xD;
          -  A liaison with the coordinating or principal investigator, which could likely&#xD;
             influence the decision to participate in this study voluntarily (in concordance with&#xD;
             the World Meteorological Organization (WMO) -article 5);&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GM de Boer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Franciscus Gasthuis Rotterdam</affiliation>
  </overall_official>
  <overall_official>
    <last_name>GJ Braunstahl, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Franciscus Gasthuis Rotterdam</affiliation>
  </overall_official>
  <overall_official>
    <last_name>GA Tramper, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Franciscus Gasthuis Rotterdam</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Franciscus Gasthuis</name>
      <address>
        <city>Rotterdam</city>
        <state>Zuid-Holland</state>
        <zip>3045PM</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>August 13, 2020</last_update_submitted>
  <last_update_submitted_qc>August 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Franciscus Gasthuis</investigator_affiliation>
    <investigator_full_name>Gerdien Tramper</investigator_full_name>
    <investigator_title>MD PhD</investigator_title>
  </responsible_party>
  <keyword>asthma</keyword>
  <keyword>age of onset</keyword>
  <keyword>inflammation</keyword>
  <keyword>comorbidity</keyword>
  <keyword>microbiome</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>Undecided</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/NCT03278561
org study id: GRANDMA
nct id: NCT03278561
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A cross-sectional study in asthma patients to determine if a late age of onset asthma (start
      symptoms >18 years old), is associated with more persistent airway/systemic inflammation,
      worse asthma control, more co-morbidity, a different microbiome and poorer quality of life
      despite the use of optimized asthma therapy.
For ages, asthma has been considered a disease for children and young adults. However,
      nowadays 30% of all asthma patients is over 50 years old. Asthma in the elderly is generally
      more severe and approximately 50% of all deaths drom asthma occur in this age group. With
      rapid aging of the global population, the burden of asthma in the elderly will further
      increase.

      Asthma is a heterogeneous disease and the question is whether asthma in the elderly can be
      considered the same disease as asthma in children and young adults. The pathophysiology and
      risk factors of asthma in the elderly are still not completely understood. Good
      characterization of asthma in the elderly requires clinical phenotyping as well as a thorough
      analysis of the underlying cellular and molecular mechanisms. It is hypothesized that in
      older asthma patients, a late age of onset (start asthma symptoms >18 years) is associated
      with more persistent airway/systemic inflammation, worse asthma control, more co-morbidity
      and poorer quality of life despite the use of optimized asthma therapy.
observational model: Cohort
time perspective: Cross-Sectional
measure: Differences in number and activation status of inflammatory cells in sputum and blood
time frame: 1 month
description: To compare the differences in number and activation status of inflammatory cells in sputum and blood of different subgroups of asthmatics.)
measure: Interleukin cell type 2 (ILC2) correlation and disease phenotype
time frame: 1 month
description: To find correlations between ILC2 numbers and characteristics and immunological and clinical disease phenotype. -
measure: Hair cortisol
time frame: 1 month
description: Detection of cortisol levels in hair, to determine a possible method to check Inhaled corticosteroid (ICS) adherence.
measure: Inflammatory profile
time frame: 1 month
description: To measure physiological factors (lung function, activity level) and relate them to inflammatory profile.
measure: Selfmanagement / coping strategies
time frame: 1 month
description: To investigate the relationship between duration and onset of asthma and self-management/coping strategies of patients.
measure: The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.
time frame: 1 month
description: The effect of aging on inflammation, physiology, psychology and co-morbidities in asthma.
measure: Detection of different microbiome subgroups of asthmatics and compare with controls.
time frame: 1 month
description: Detection of microflora/microbiome pattern in sputum and faeces in different subgroups of asthmatics and compare with controls.
arm group label: Early onset asthma
description: Sputum induction according to the European Respiratory Society (ERS) protocol. A blood sample of 100ml will be taken.
arm group label: Late onset asthma
description: Sputum induction according to the ERS protocol. A blood sample of 100ml will be taken.
arm group label: No pulmonary disease
description: Sputum induction according to the ERS protocol. A blood sample of 100ml will be taken.
intervention type: Procedure
intervention name: Sputum induction
description: Sputum induction according to the ERS protocol
arm group label: Early onset asthma
arm group label: Late onset asthma
arm group label: No pulmonary disease
intervention type: Procedure
intervention name: Blood sample
description: A blood sample of 100ml will be taken.
arm group label: Early onset asthma
arm group label: Late onset asthma
arm group label: No pulmonary disease
sputum, blood, NP swab, feces
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GM de Boer, MD
role: Principal Investigator
affiliation: Franciscus Gasthuis Rotterdam
last name: GJ Braunstahl, MD, PhD
role: Principal Investigator
affiliation: Franciscus Gasthuis Rotterdam
last name: GA Tramper, MD, PhD
role: Principal Investigator
affiliation: Franciscus Gasthuis Rotterdam
facility: 
country: Netherlands
responsible party type: Sponsor-Investigator
investigator affiliation: Franciscus Gasthuis
investigator full name: Gerdien Tramper
investigator title: MD PhD
mesh term: Asthma
sharing ipd: Undecided