<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/NCT01693965</url>
  </required_header>
  <id_info>
    <org_study_id>2012-A00601-42</org_study_id>
    <secondary_id>2012-14</secondary_id>
    <nct_id>NCT01693965</nct_id>
  </id_info>
  <brief_title>Clinical Course and Changes in the Respiratory Microbiota Based on Antibiotic Treatment in Patients With Cystic Fibrosis</brief_title>
  <official_title>Clinical Course and Changes in the Respiratory Microbiota Based on Antibiotic Treatment in Patients With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique Hopitaux De Marseille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique Hopitaux De Marseille</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Bronchopulmonary infection is the most common and serious complication in the evolutionary&#xD;
      course of cystic fibrosis (CF). Administration of antibiotics adapted to infecting pathogens&#xD;
      is one of the key issues for its management. However, more than half of patients with CF have&#xD;
      chronic respiratory infections for which infectious agent remains unknown leading to&#xD;
      empirical antibiotic therapies that are not adapted to the causative agents. Recently, new&#xD;
      technologies have been applied for the description and characterization of microbial agents&#xD;
      in CF patients including molecular biology techniques that allowed us to detect and to&#xD;
      identify new and/or emerging pathogens. Moreover, more sophisticated molecular techniques&#xD;
      such as pyrosequencing and PCR amplification and cloning lead us to demonstrate the huge&#xD;
      microbial diversity associated with chronic bronchopulmonary infections in this population.&#xD;
      Otherwise, a metagenomic approach revealed the extraordinary complexity of the respiratory&#xD;
      flora in these patients and, somewhat unexpected, abundance of anaerobes, viruses, and&#xD;
      bacteriophages. In addition, it has been shown that some antibiotics commonly used in&#xD;
      clinical practice for the treatment of respiratory infections were able to induce these&#xD;
      bacteriophages, suggesting the existence of lateral gene transfer by transduction. The human&#xD;
      microbiome is the set of microbial communities associated with the human body and represents&#xD;
      all living microorganisms in the body. Its role in the immunity development has recently been&#xD;
      demonstrated suggesting that changes in this ecosystem play a critical role in evolution of&#xD;
      several human diseases. For example, in obesity it has been shown that there is a&#xD;
      relationship between the intestinal human microbiota and nutritional and metabolic status of&#xD;
      the hosts and specific alterations of these intestinal microbiota may represent a metagenomic&#xD;
      signature of this disease. Evolution of the respiratory microbiota in patients with cystic&#xD;
      fibrosis, whose nutritional status is often impaired (chronic malnutrition due to disorder of&#xD;
      digestive absorption) and receiving regular antibiotic treatments remains unknown to date.&#xD;
      Characterization of this ecosystem and its role is a critical step to understand the&#xD;
      evolutionary course of the disease.&#xD;
&#xD;
      The main objective of this seminal study is to describe and to characterize the respiratory&#xD;
      microbiota from sputum samples obtained from a limited number of selected patients with CF&#xD;
      from 5 regional care centers (CRCM) from South of France (Mucomed network) (2 patients per&#xD;
      center : 6 adults and 4 children), with similar clinical, microbiological and functional&#xD;
      status before and after a cure of antibiotics. Different microbiological tools will be used&#xD;
      including axenic culture systems, co-culture on amoebae in order to to isolate and to&#xD;
      identify the microbial communities. Identification of bacteria will be done using MALDI-TOF&#xD;
      mass spectrometry and/or molecular techniques. Moreover, 16S rRNA PCR amplification followed&#xD;
      by cloning and sequencing of PCR products from the same sputum sample will be carried out to&#xD;
      identify and to compare the bacterial species identified using molecular methods. In a second&#xD;
      step, once the respiratory microbiota was characterized, it will be interesting to develop a&#xD;
      dedicated microarray that will allow to detect all the bacteria identified in the first stage&#xD;
      of the project and to assess its relevance on a larger cohort of patients with CF by studying&#xD;
      the correlation between the respiratory microbiota and clinical status of patients according&#xD;
      to the prescribed antibiotic treatments.&#xD;
&#xD;
      This study will open new clinical perspectives and will help us to determine the potential&#xD;
      role of antibiotics on the microbiota evolution during treatment according to regional health&#xD;
      care practices. This will contribute to better understand the role of the microbiota in the&#xD;
      evolution of these chronic respiratory infections. It could be the first step for innovative&#xD;
      therapeutic strategies, taking into account the balance of complex microbial flora and&#xD;
      possibly evolving according to antibiotic therapies. It could also form part of a larger&#xD;
      preventive strategy against transmission of specific pathogens in CF.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 22, 2013</start_date>
  <completion_date type="Actual">August 3, 2023</completion_date>
  <primary_completion_date type="Actual">November 12, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A taking of expectorations</measure>
    <time_frame>3 years</time_frame>
    <description>describe and characterize the respiratory microbiota</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Bronchopulmonary Infection</condition>
  <arm_group>
    <arm_group_label>sputum samples</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>sputum samples</intervention_name>
    <arm_group_label>sputum samples</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects achieves of cystic fibrosis followed regularly in one 5 Grown-up CRCM or&#xD;
             Children involved in the study&#xD;
&#xD;
               -  Inclusions of 10 patients at the rate of 2 subjects by center (6 adults and 4&#xD;
                  children). The adults (&gt; 18 years) will be patients followed in the CRCM of&#xD;
                  grown-up Marseille (2), of Giens-Hyères (1), Montpelier (1) and Nice (2); 4&#xD;
                  children ( 11 - 17 years) will be followed in the CRCM of Marseille children (2),&#xD;
                  of Giens-Hyères (1) and Montpelier (1).&#xD;
&#xD;
               -  Patients having a clinical status (appeal(recourse) to 1 cure / year of&#xD;
                  antibiotics in IV), functional (VEMS = 30 % of the theoretical value) and&#xD;
                  microbiological identical,&#xD;
&#xD;
               -  Patients presenting a bronchial colonization to Pseudomonas aeruginosa known for&#xD;
                  at least 3 months, sensitive to the tobramycine and to the ceftazidime, not&#xD;
                  having received from cure of antibiotic IV during month preceding the inclusion&#xD;
                  in the study.&#xD;
&#xD;
               -  Patients not presenting fungal concommitante colonization or for at least 3&#xD;
                  months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  not affected Subject of cystic fibrosis&#xD;
&#xD;
               -  Subject achieves of cystic fibrosis followed regularly in another center than the&#xD;
                  one 4 participating CRCM&#xD;
&#xD;
               -  Subject achieves of cystic fibrosis among which the clinical status and the&#xD;
                  initial bronchial colonization is not known&#xD;
&#xD;
               -  Subject having meant in the oral its opposition has the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>11 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>BERNARD BELAIGUES</last_name>
    <role>Study Director</role>
    <affiliation>Assistance Publique Hopitaux De Marseille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assistance Publique Hopitaux de Marseille</name>
      <address>
        <city>Marseille</city>
        <zip>13354</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2012</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</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>Cystic Fibrosis</mesh_term>
    <mesh_term>Disease Progression</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/NCT01693965
org study id: 2012-A00601-42
secondary id: 2012-14
nct id: NCT01693965
lead sponsor: 
has dmc: No
Bronchopulmonary infection is the most common and serious complication in the evolutionary
      course of cystic fibrosis (CF). Administration of antibiotics adapted to infecting pathogens
      is one of the key issues for its management. However, more than half of patients with CF have
      chronic respiratory infections for which infectious agent remains unknown leading to
      empirical antibiotic therapies that are not adapted to the causative agents. Recently, new
      technologies have been applied for the description and characterization of microbial agents
      in CF patients including molecular biology techniques that allowed us to detect and to
      identify new and/or emerging pathogens. Moreover, more sophisticated molecular techniques
      such as pyrosequencing and PCR amplification and cloning lead us to demonstrate the huge
      microbial diversity associated with chronic bronchopulmonary infections in this population.
      Otherwise, a metagenomic approach revealed the extraordinary complexity of the respiratory
      flora in these patients and, somewhat unexpected, abundance of anaerobes, viruses, and
      bacteriophages. In addition, it has been shown that some antibiotics commonly used in
      clinical practice for the treatment of respiratory infections were able to induce these
      bacteriophages, suggesting the existence of lateral gene transfer by transduction. The human
      microbiome is the set of microbial communities associated with the human body and represents
      all living microorganisms in the body. Its role in the immunity development has recently been
      demonstrated suggesting that changes in this ecosystem play a critical role in evolution of
      several human diseases. For example, in obesity it has been shown that there is a
      relationship between the intestinal human microbiota and nutritional and metabolic status of
      the hosts and specific alterations of these intestinal microbiota may represent a metagenomic
      signature of this disease. Evolution of the respiratory microbiota in patients with cystic
      fibrosis, whose nutritional status is often impaired (chronic malnutrition due to disorder of
      digestive absorption) and receiving regular antibiotic treatments remains unknown to date.
      Characterization of this ecosystem and its role is a critical step to understand the
      evolutionary course of the disease.

      The main objective of this seminal study is to describe and to characterize the respiratory
      microbiota from sputum samples obtained from a limited number of selected patients with CF
      from 5 regional care centers (CRCM) from South of France (Mucomed network) (2 patients per
      center : 6 adults and 4 children), with similar clinical, microbiological and functional
      status before and after a cure of antibiotics. Different microbiological tools will be used
      including axenic culture systems, co-culture on amoebae in order to to isolate and to
      identify the microbial communities. Identification of bacteria will be done using MALDI-TOF
      mass spectrometry and/or molecular techniques. Moreover, 16S rRNA PCR amplification followed
      by cloning and sequencing of PCR products from the same sputum sample will be carried out to
      identify and to compare the bacterial species identified using molecular methods. In a second
      step, once the respiratory microbiota was characterized, it will be interesting to develop a
      dedicated microarray that will allow to detect all the bacteria identified in the first stage
      of the project and to assess its relevance on a larger cohort of patients with CF by studying
      the correlation between the respiratory microbiota and clinical status of patients according
      to the prescribed antibiotic treatments.

      This study will open new clinical perspectives and will help us to determine the potential
      role of antibiotics on the microbiota evolution during treatment according to regional health
      care practices. This will contribute to better understand the role of the microbiota in the
      evolution of these chronic respiratory infections. It could be the first step for innovative
      therapeutic strategies, taking into account the balance of complex microbial flora and
      possibly evolving according to antibiotic therapies. It could also form part of a larger
      preventive strategy against transmission of specific pathogens in CF.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: A taking of expectorations
time frame: 3 years
description: describe and characterize the respiratory microbiota
arm group label: sputum samples
arm group type: Other
intervention type: Other
intervention name: sputum samples
arm group label: sputum samples
criteria: 
gender: All
minimum age: 11 Years
maximum age: N/A
healthy volunteers: No
last name: BERNARD BELAIGUES
role: Study Director
affiliation: Assistance Publique Hopitaux De Marseille
facility: 
country: France
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Disease Progression