<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/NCT03767673</url>
  </required_header>
  <id_info>
    <org_study_id>1.1</org_study_id>
    <nct_id>NCT03767673</nct_id>
  </id_info>
  <brief_title>Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia</brief_title>
  <official_title>Examination of the Cardiorespiratory Performance Capacity and Pulmonary Microbiome in Patients Following Surgical Repair of Esophageal Atresia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</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 majority of the clinical research on esophageal atresia focuses on the upper&#xD;
      gastrointestinal tract. However, the trachea and the lung are also affected in many of these&#xD;
      children, so that a lifelong pulmonary impairment may result. The importance of respiratory&#xD;
      function in the context of follow-up of these patients has therefore been increasingly&#xD;
      recognized in recent years. Scientific work has shown significantly, that patients following&#xD;
      esophageal atresia repair develop respiratory symptoms more frequently than the normal&#xD;
      population. Mild impairment of the pulmonary function in adolescence and adulthood was&#xD;
      demonstrated in some studies, but to date, there is no exact idea about the relationship&#xD;
      between early childhood disease progression and later pulmonary impairment. Only a few&#xD;
      scientific papers have dealt with the effect of impaired pulmonary function on the physical&#xD;
      capacity of these adolescents and adults. Most of these studies show small case numbers,&#xD;
      inconclusive stress tests, and divergent results.&#xD;
&#xD;
      The aim of this prospective study is to investigate the cardiopulmonary performance capacity&#xD;
      and the pulmonary microbiome of adolescent and adult patients with corrected esophageal&#xD;
      atresia and to compare the results with a control group. Another focus of the investigators&#xD;
      is on the composition of the pulmonary microbiome of the participants. Changes of the&#xD;
      pulmonary microbiome and the influence on the cardio-pulmonary performance capacity have not&#xD;
      yet been investigated. Furthermore, it should be investigated whether the treatment measures&#xD;
      and a complicated disease course in the neonatal period have long-term effects on lung&#xD;
      function, exercise capacity and composition of the microbiome in the lungs.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 10, 2017</start_date>
  <completion_date type="Anticipated">September 2, 2019</completion_date>
  <primary_completion_date type="Anticipated">April 6, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Control group: Age and sex matched healthy volunteers.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Pulmonary microbiome (16S rDNA profiling) - Alpha diversity</measure>
    <time_frame>1 year</time_frame>
    <description>Determination of alpha diversity (Chao1 Test) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of Alpha diversity (Chao1 Analysis) between patients after repair of esophageal atresia and age and sex matched healthy controls.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary microbiome (16S rDNA profiling) - Beta diversity</measure>
    <time_frame>1 year</time_frame>
    <description>Determination of beta diversity (unweighted UniFrac test) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of beta-diversity (Unweighted UniFrac Analysis) between patients after repair of esophageal atresia and age and sex matched healthy controls.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary microbiome (16S rDNA profiling) - relative bacterial abundance</measure>
    <time_frame>1 year</time_frame>
    <description>Determination of relative bacterial abundance (in per Cent) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of relative bacterial abundance (Mann-Whitney-U-Test) between patients after repair of esophageal atresia and age and sex matched healthy controls.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum oxygen uptake (ergospirometer)</measure>
    <time_frame>1 year</time_frame>
    <description>Maximum oxygen uptake (corrected for age, gender and body weight ) as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Performance (ergospirometer)</measure>
    <time_frame>1 year</time_frame>
    <description>Maximum performance as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital capacity (spirometry)</measure>
    <time_frame>1 year</time_frame>
    <description>Vital capacity as determined by spirometry. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Esophageal Atresia</condition>
  <arm_group>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients older than 12 years following surgical repair of congenital esophageal atresia will be included after written informed consent. Patients will be subjected to spirometry to determine their age, weight (determined by Kilogram (kg) on a medical weight scale) and Vital Capacity before (initial Spirometry) and after (final Spirometry) exercise performance testing. Bicycle ergospirometer will be applied to determine the Maximum Oxygen Uptake and the Maximum Performance. Thereafter deep induced sputum will be harvested for measurements of the pulmonary microbiome (Pulmonary Microbiome 16S rDNA profiling).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Age and sex matched adolescents will be recruited as control group and will be included after written informed consent. Adolescents will be subjected to spirometry to determine their age, weight (determined by Kilogram on a medical weight scale) and Vital Capacity before (initial Spirometry) and after (final Spirometry) exercise performance testing. Bicycle ergospirometer will be applied to determine the Maximum Oxygen Uptake and the Maximum Performance. Thereafter deep induced sputum will be harvested for measurements of the pulmonary microbiome (Pulmonary Microbiome 16S rDNA profiling).</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Initial Spirometry</intervention_name>
    <description>Determination of Vital Capacity by spirometry before (within 30 minutes) spiroergometry. Measurements will be performed in both groups.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Final Spirometry</intervention_name>
    <description>Determination of Vital Capacity by spirometry after (within 30 minutes) spiroergometry. Measurements will be performed in both groups.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pulmonary microbiome (16S rDNA profiling)</intervention_name>
    <description>Harvesting of deep induced sputum and determination of the airway microbiome by 16S ribosomal RNA (rRNA) pyrosequencing. Evaluation of alpha and beta diversity and relative bacterial abundance at the genus level. Measurements will be performed in both groups (samples will be harvested within 30 minutes after spiroergometry).</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Maximum oxygen uptake</intervention_name>
    <description>Determination of the maximum oxygen uptake (ml/kg/min) corrected for gender, age and body weight by bicycle spiroergometry. Measurements will be performed in both groups.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Maximum performance</intervention_name>
    <description>Determination of the maximum performance (W/kg) corrected for body weight by bicycle spiroergometry. Measurements will be performed in both groups.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>weight</intervention_name>
    <description>Determined by Kilogram on a medical weight scale</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>age</intervention_name>
    <description>Determination of age by patient's Report and past medical history</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Patients after esophageal atresia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age from 12 years&#xD;
&#xD;
          -  Status post surgical correction of esophageal atresia with and without fistula&#xD;
&#xD;
          -  Granted consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute infections within the last 14 days&#xD;
&#xD;
          -  Other associated serious malformations&#xD;
&#xD;
          -  Acute, temporary respiratory complaints (cough, allergies etc.)&#xD;
&#xD;
          -  Physical and mental illnesses or disabilities that do not allow the examination to be&#xD;
             carried out&#xD;
&#xD;
          -  non-granted consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jana Windhaber, MD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Holger Till, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christoph Arneitz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jana Windhaber, MD.</last_name>
    <phone>01143316358</phone>
    <phone_ext>83770</phone_ext>
    <email>jana.windhaber@klinikum-graz.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Christoph Arneitz, MD.</last_name>
    <phone>01143316358</phone>
    <phone_ext>80358</phone_ext>
    <email>christoph.arneitz@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <zip>8010</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jana Windhaber, MD</last_name>
      <phone>01143316385</phone>
      <phone_ext>83770</phone_ext>
      <email>jana.windhaber@medunigraz.at</email>
    </contact>
    <contact_backup>
      <last_name>Christoph Arneitz, MD</last_name>
      <phone>01143316385</phone>
      <phone_ext>80358</phone_ext>
      <email>christoph.arneitz@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>July 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>December 5, 2018</last_update_submitted>
  <last_update_submitted_qc>December 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</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>Esophageal Atresia</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/NCT03767673
org study id: 1.1
nct id: NCT03767673
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The majority of the clinical research on esophageal atresia focuses on the upper
      gastrointestinal tract. However, the trachea and the lung are also affected in many of these
      children, so that a lifelong pulmonary impairment may result. The importance of respiratory
      function in the context of follow-up of these patients has therefore been increasingly
      recognized in recent years. Scientific work has shown significantly, that patients following
      esophageal atresia repair develop respiratory symptoms more frequently than the normal
      population. Mild impairment of the pulmonary function in adolescence and adulthood was
      demonstrated in some studies, but to date, there is no exact idea about the relationship
      between early childhood disease progression and later pulmonary impairment. Only a few
      scientific papers have dealt with the effect of impaired pulmonary function on the physical
      capacity of these adolescents and adults. Most of these studies show small case numbers,
      inconclusive stress tests, and divergent results.

      The aim of this prospective study is to investigate the cardiopulmonary performance capacity
      and the pulmonary microbiome of adolescent and adult patients with corrected esophageal
      atresia and to compare the results with a control group. Another focus of the investigators
      is on the composition of the pulmonary microbiome of the participants. Changes of the
      pulmonary microbiome and the influence on the cardio-pulmonary performance capacity have not
      yet been investigated. Furthermore, it should be investigated whether the treatment measures
      and a complicated disease course in the neonatal period have long-term effects on lung
      function, exercise capacity and composition of the microbiome in the lungs.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
masking description: Control group: Age and sex matched healthy volunteers.
measure: Pulmonary microbiome (16S rDNA profiling) - Alpha diversity
time frame: 1 year
description: Determination of alpha diversity (Chao1 Test) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of Alpha diversity (Chao1 Analysis) between patients after repair of esophageal atresia and age and sex matched healthy controls.
measure: Pulmonary microbiome (16S rDNA profiling) - Beta diversity
time frame: 1 year
description: Determination of beta diversity (unweighted UniFrac test) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of beta-diversity (Unweighted UniFrac Analysis) between patients after repair of esophageal atresia and age and sex matched healthy controls.
measure: Pulmonary microbiome (16S rDNA profiling) - relative bacterial abundance
time frame: 1 year
description: Determination of relative bacterial abundance (in per Cent) at the genus level of deep induced Sputum by 16S rDNA profiling. Comparison of relative bacterial abundance (Mann-Whitney-U-Test) between patients after repair of esophageal atresia and age and sex matched healthy controls.
measure: Maximum oxygen uptake (ergospirometer)
time frame: 1 year
description: Maximum oxygen uptake (corrected for age, gender and body weight ) as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.
measure: Maximum Performance (ergospirometer)
time frame: 1 year
description: Maximum performance as determined by bicycle ergospirometer. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.
measure: Vital capacity (spirometry)
time frame: 1 year
description: Vital capacity as determined by spirometry. Comparison of parameters between patients after repair of esophageal atresia and age and sex matched healthy controls.
arm group label: Patients after esophageal atresia
arm group type: Experimental
description: Patients older than 12 years following surgical repair of congenital esophageal atresia will be included after written informed consent. Patients will be subjected to spirometry to determine their age, weight (determined by Kilogram (kg) on a medical weight scale) and Vital Capacity before (initial Spirometry) and after (final Spirometry) exercise performance testing. Bicycle ergospirometer will be applied to determine the Maximum Oxygen Uptake and the Maximum Performance. Thereafter deep induced sputum will be harvested for measurements of the pulmonary microbiome (Pulmonary Microbiome 16S rDNA profiling).
arm group label: Control group
arm group type: Active Comparator
description: Age and sex matched adolescents will be recruited as control group and will be included after written informed consent. Adolescents will be subjected to spirometry to determine their age, weight (determined by Kilogram on a medical weight scale) and Vital Capacity before (initial Spirometry) and after (final Spirometry) exercise performance testing. Bicycle ergospirometer will be applied to determine the Maximum Oxygen Uptake and the Maximum Performance. Thereafter deep induced sputum will be harvested for measurements of the pulmonary microbiome (Pulmonary Microbiome 16S rDNA profiling).
intervention type: Diagnostic Test
intervention name: Initial Spirometry
description: Determination of Vital Capacity by spirometry before (within 30 minutes) spiroergometry. Measurements will be performed in both groups.
arm group label: Control group
arm group label: Patients after esophageal atresia
intervention type: Diagnostic Test
intervention name: Final Spirometry
description: Determination of Vital Capacity by spirometry after (within 30 minutes) spiroergometry. Measurements will be performed in both groups.
arm group label: Control group
arm group label: Patients after esophageal atresia
intervention type: Diagnostic Test
intervention name: Pulmonary microbiome (16S rDNA profiling)
description: Harvesting of deep induced sputum and determination of the airway microbiome by 16S ribosomal RNA (rRNA) pyrosequencing. Evaluation of alpha and beta diversity and relative bacterial abundance at the genus level. Measurements will be performed in both groups (samples will be harvested within 30 minutes after spiroergometry).
arm group label: Control group
arm group label: Patients after esophageal atresia
intervention type: Diagnostic Test
intervention name: Maximum oxygen uptake
description: Determination of the maximum oxygen uptake (ml/kg/min) corrected for gender, age and body weight by bicycle spiroergometry. Measurements will be performed in both groups.
arm group label: Control group
arm group label: Patients after esophageal atresia
intervention type: Diagnostic Test
intervention name: Maximum performance
description: Determination of the maximum performance (W/kg) corrected for body weight by bicycle spiroergometry. Measurements will be performed in both groups.
arm group label: Control group
arm group label: Patients after esophageal atresia
intervention type: Diagnostic Test
intervention name: weight
description: Determined by Kilogram on a medical weight scale
arm group label: Control group
arm group label: Patients after esophageal atresia
intervention type: Other
intervention name: age
description: Determination of age by patient's Report and past medical history
arm group label: Control group
arm group label: Patients after esophageal atresia
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jana Windhaber, MD
role: Study Director
affiliation: Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria
last name: Holger Till, MD
role: Study Chair
affiliation: Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria
last name: Christoph Arneitz, MD
role: Principal Investigator
affiliation: Department of Paediatric and Adolescent Surgery, Medical University of Graz, Austria
last name: Jana Windhaber, MD.
phone: 01143316358
phone ext: 83770
email: jana.windhaber@klinikum-graz.at
last name: Christoph Arneitz, MD.
phone: 01143316358
phone ext: 80358
email: christoph.arneitz@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Austria
responsible party type: Sponsor
mesh term: Esophageal Atresia