<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/NCT04458129</url>
  </required_header>
  <id_info>
    <org_study_id>CHUBX 2019/25</org_study_id>
    <nct_id>NCT04458129</nct_id>
  </id_info>
  <brief_title>Polyethylene Glycol and Intestinal Inflammation in Cystic Fibrosis</brief_title>
  <acronym>MUCOLAX</acronym>
  <official_title>EFFECT OF POLYETHYLENE GLYCOL TREATMENT ON INTESTINAL INFLAMMATION ASSOCIATED WITH CYSTIC FIBROSIS IN CHILDREN</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Bordeaux</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Bordeaux</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 main objective of the study is to evaluate the effectiveness of polyethylene glycol&#xD;
      treatment on intestinal inflammation in children with cystic fibrosis. In this test, a method&#xD;
      adapted from the Fleming one-step scheme will be used. The success rate is measured by the&#xD;
      proportion of patients with fecal calprotectin levels &lt; 250 µg/g at 3 months after treatment&#xD;
      initiation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cystic fibrosis is one of the most frequent serious genetic diseases in France (7000&#xD;
      patients). It is the consequence of mutations in the CFTR gene, encoding a protein involved&#xD;
      in the hydro-electrolytic balance of secretions. Beyond the well-known lung damage in these&#xD;
      patients, intestinal inflammation is present in the majority of patients.&#xD;
&#xD;
      While advances in the management of cystic fibrosis are increasing patient life expectancy,&#xD;
      other issues are emerging, including the impact of this chronic intestinal inflammation on&#xD;
      the nutritional status and high risk of digestive cancers (Maisonneuve, 2013; Garg and Ooi,&#xD;
      2017; Yamada, 2018).&#xD;
&#xD;
      Currently, no management is proposed to treat this intestinal inflammation. The use of&#xD;
      laxatives to fluidize digestive secretions and restore a digestive ecosystem close to the&#xD;
      healthy subject could constitute a new therapeutic approach to this intestinal inflammation,&#xD;
      as previously shown in the mouse model of cystic fibrosis (De Lisle, 2007). However, to date,&#xD;
      to the investigator's knowledge, no studies have evaluated the effect of laxative treatment&#xD;
      on intestinal inflammation of cystic fibrosis in humans.&#xD;
&#xD;
      This study is a bi-centric, non-comparative, prospective study for a phase II trial according&#xD;
      to a Fleming scheme.&#xD;
&#xD;
      Study participants will take a 3-month laxative treatment with polyethylene glycol for 3&#xD;
      months. In addition to the inclusion visit, a follow-up visit will take place at 3 months and&#xD;
      3 intermediate telephone calls will be made to ensure efficacy, tolerance and compliance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 8, 2020</start_date>
  <completion_date type="Anticipated">July 8, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 8, 2022</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Bi-centric, non-comparative, prospective, Phase II trial according to a Fleming scheme.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Impact of a 3-month polyethylene glycol treatment on intestinal inflammation assessed by measurement of fecal calprotectin (µg / g) by an ELISA biological test</measure>
    <time_frame>3 months after the inclusion visit i.e. 3 months after the initiation of treatment with polyethylene glycol</time_frame>
    <description>proportion of patients with fecal calprotectin &lt;250 µg / g measured by an ELISA test 3 months after initiation of treatment with polyethylene glycol, testifying to the absence of intestinal inflammation or slight inflammation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evolution of the digestive inflammatory response, assessed by measurement of fecal calprotectin (µg / g)</measure>
    <time_frame>Change from Baseline fecal calprotectin measurement at 3 months</time_frame>
    <description>Evolution of the digestive inflammatory response, assessed by measurement of fecal calprotectin (µg / g) by an ELISA biological test between the initiation of treatment (D0) and 3 months of treatment with polyethylene glycol (M3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the digestive inflammatory response, assessed by Analysis of the expression of genes involved in the inflammatory and pro-oncogenic response</measure>
    <time_frame>Change from Baseline measurement at 3 months</time_frame>
    <description>Analysis of the expression of genes involved in the inflammatory and pro-oncogenic response, using NanoString Technology and the nCounters® PanCancer Immune Profiling Panel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the digestive symptoms, assessed by the JenAbdomen CF-score</measure>
    <time_frame>Change from Baseline measurement at 3 months</time_frame>
    <description>The JenAbdomen CF-score has been described in the following publication Tabori H. et al. Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings. PloS One 12,e0174463 (2017).&#xD;
the JenAbdomen CF-Score is based on a CF patient-reported outcome measure (PROM) that includes all relevant gastrointestinal symptoms and their impact on subjective quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the quality of life scores, assessed by the CFQ-R questionnaire</measure>
    <time_frame>Change from Baseline measurement at 3 months</time_frame>
    <description>The CFQ-R questionnaire has been described in the following publication: Modi, A. C. &amp; Quittner, A. L. Validation of a disease-specific measure of health-related quality of life for children with cystic fibrosis. J. Pediatr. Psychol. 28, 535-545 (2003).&#xD;
The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a disease-specific health-related quality of life (HRQOL) measure for children, adolescents and adults with cystic fibrosis (CF). It is a profile measure of HRQOL with several different domains. It has undergone extensive reliability and validity testing.&#xD;
The Cystic Fibrosis Questionnaire-Revised (CFQ-R) application calculates the score derived from the CFQ-R, on a 0-100 scale with higher scores indicating better HRQoL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the composition of the bacterial intestinal microbiota</measure>
    <time_frame>Change from Baseline measurement at 3 months</time_frame>
    <description>The composition of the bacterial intestinal microbiota will be assessed by High-throughput sequencing and phylogenetic allocation of the bacterial flora (on MiSeq, from Illumina®)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the composition of the fungal intestinal microbiota</measure>
    <time_frame>Change from Baseline measurement at 3 months</time_frame>
    <description>The composition of the fungal intestinal microbiota will be assessed by high-throughput sequencing and phylogenetic allocation of the fungal flora (on MiSeq, from Illumina®)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the pulmonary inflammation, assessed by the dosage of calprotectin in the sputum</measure>
    <time_frame>Change from Baseline measurement at 3 months</time_frame>
    <description>Evolution of the Pulmonary inflammation will be assessed by measurement of salivary calprotectin (µg / g) by an ELISA biological test between the initiation of treatment (D0) and 3 months of treatment with polyethylene glycol (M3)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">23</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Polyethylene glycol treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study participants will take a 3-month laxative treatment with polyethylene glycol for 3 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Treatment with polyethylene glycol (Macrogol 4000)</intervention_name>
    <description>3-month treatment with polyethylene glycol (Macrogol 4000), powder for oral solution, in 4g and 10g sachets. Dosage of 0.7 g/kg/day, with a maximum dose of 20 g/day.</description>
    <arm_group_label>Polyethylene glycol treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 4 years old and &lt;18 years old ;&#xD;
&#xD;
          -  Patient with cystic fibrosis (sweat test &gt; 60 mmol/l and/or molecular biology&#xD;
             identifying mutations in the CFTR gene) with associated pancreatic insufficiency&#xD;
             (fecal elastase &lt;100 µg/g);&#xD;
&#xD;
          -  With a rapid calprotectin assay result via the IBDoc test (Bühlmann®) superior or&#xD;
             equal to 250 µg/g;&#xD;
&#xD;
          -  Person affiliated or benefiting from a social security scheme;&#xD;
&#xD;
          -  Free, informed and written consent signed by the holders of parental authority and the&#xD;
             investigator before any examination required by the research and oral and/or written&#xD;
             consent by the participant (depending on his/her age).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Ongoing processing that can modulate the functionality of the CFTR (such as&#xD;
             lumacaftor-ivacaftor protein therapy);&#xD;
&#xD;
          -  Patient already on polyethylene glycol or other laxative within 3 months before the&#xD;
             inclusion visit;&#xD;
&#xD;
          -  Patient with diarrhea at inclusion (diarrhea will be defined as the presence of 3 or&#xD;
             more stools / day in the 7 days prior to the inclusion visit);&#xD;
&#xD;
          -  Acute viral or bacterial diarrhea in the month prior to the inclusion visit&#xD;
             (associated with fever);&#xD;
&#xD;
          -  Cure of oral or intravenous antibiotics or antifungals in the month preceding the&#xD;
             collection of samples;&#xD;
&#xD;
          -  Change in background treatment in the month prior to the inclusion visit (oral or&#xD;
             inhaled corticosteroid therapy, azithromycin, inhaled antibiotic therapy, inhaled&#xD;
             antifungal agent, proton pump inhibitors);&#xD;
&#xD;
          -  Taking probiotics in the month before the inclusion visit;&#xD;
&#xD;
          -  Transplanted patient (on immunosuppressants);&#xD;
&#xD;
          -  Patient with IBD or celiac disease;&#xD;
&#xD;
          -  Patient with digestive perforation or risk of digestive perforation;&#xD;
&#xD;
          -  Patient with ileus or suspicion of intestinal obstruction, symptomatic stenosis;&#xD;
&#xD;
          -  History of hypersensitivity to macrogol or any of the excipients&#xD;
&#xD;
          -  Holders of parental authority enjoying judicial protection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie M MITTAINE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU de Toulouse - Hôpital des Enfants - Centre de Ressources et de Compétences de la Mucoviscidose (CRCM) pédiatrique</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Raphaël R ENAUD, MD</last_name>
    <phone>0556799824</phone>
    <email>raphael.enaud@chu-bordeaux.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Aurore CAPELLI, PhD</last_name>
    <phone>0557820877</phone>
    <email>aurore.capelli@chu-bordeaux.fr</email>
  </overall_contact_backup>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>July 2, 2020</last_update_submitted>
  <last_update_submitted_qc>July 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <keyword>intestinal inflammation</keyword>
  <keyword>fecal calprotectin</keyword>
  <keyword>microbiota</keyword>
  <keyword>children</keyword>
  <keyword>polyethylene glycol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
    <mesh_term>Inflammation</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/NCT04458129
org study id: CHUBX 2019/25
nct id: NCT04458129
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of the study is to evaluate the effectiveness of polyethylene glycol
      treatment on intestinal inflammation in children with cystic fibrosis. In this test, a method
      adapted from the Fleming one-step scheme will be used. The success rate is measured by the
      proportion of patients with fecal calprotectin levels < 250 µg/g at 3 months after treatment
      initiation.
Cystic fibrosis is one of the most frequent serious genetic diseases in France (7000
      patients). It is the consequence of mutations in the CFTR gene, encoding a protein involved
      in the hydro-electrolytic balance of secretions. Beyond the well-known lung damage in these
      patients, intestinal inflammation is present in the majority of patients.

      While advances in the management of cystic fibrosis are increasing patient life expectancy,
      other issues are emerging, including the impact of this chronic intestinal inflammation on
      the nutritional status and high risk of digestive cancers (Maisonneuve, 2013; Garg and Ooi,
      2017; Yamada, 2018).

      Currently, no management is proposed to treat this intestinal inflammation. The use of
      laxatives to fluidize digestive secretions and restore a digestive ecosystem close to the
      healthy subject could constitute a new therapeutic approach to this intestinal inflammation,
      as previously shown in the mouse model of cystic fibrosis (De Lisle, 2007). However, to date,
      to the investigator's knowledge, no studies have evaluated the effect of laxative treatment
      on intestinal inflammation of cystic fibrosis in humans.

      This study is a bi-centric, non-comparative, prospective study for a phase II trial according
      to a Fleming scheme.

      Study participants will take a 3-month laxative treatment with polyethylene glycol for 3
      months. In addition to the inclusion visit, a follow-up visit will take place at 3 months and
      3 intermediate telephone calls will be made to ensure efficacy, tolerance and compliance.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Bi-centric, non-comparative, prospective, Phase II trial according to a Fleming scheme.
primary purpose: Treatment
masking: None (Open Label)
measure: Impact of a 3-month polyethylene glycol treatment on intestinal inflammation assessed by measurement of fecal calprotectin (µg / g) by an ELISA biological test
time frame: 3 months after the inclusion visit i.e. 3 months after the initiation of treatment with polyethylene glycol
description: proportion of patients with fecal calprotectin <250 µg / g measured by an ELISA test 3 months after initiation of treatment with polyethylene glycol, testifying to the absence of intestinal inflammation or slight inflammation.
measure: Evolution of the digestive inflammatory response, assessed by measurement of fecal calprotectin (µg / g)
time frame: Change from Baseline fecal calprotectin measurement at 3 months
description: Evolution of the digestive inflammatory response, assessed by measurement of fecal calprotectin (µg / g) by an ELISA biological test between the initiation of treatment (D0) and 3 months of treatment with polyethylene glycol (M3)
measure: Evolution of the digestive inflammatory response, assessed by Analysis of the expression of genes involved in the inflammatory and pro-oncogenic response
time frame: Change from Baseline measurement at 3 months
description: Analysis of the expression of genes involved in the inflammatory and pro-oncogenic response, using NanoString Technology and the nCounters® PanCancer Immune Profiling Panel
measure: Evolution of the digestive symptoms, assessed by the JenAbdomen CF-score
time frame: Change from Baseline measurement at 3 months
description: The JenAbdomen CF-score has been described in the following publication Tabori H. et al. Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings. PloS One 12,e0174463 (2017).
the JenAbdomen CF-Score is based on a CF patient-reported outcome measure (PROM) that includes all relevant gastrointestinal symptoms and their impact on subjective quality of life
measure: Evolution of the quality of life scores, assessed by the CFQ-R questionnaire
time frame: Change from Baseline measurement at 3 months
description: The CFQ-R questionnaire has been described in the following publication: Modi, A. C. & Quittner, A. L. Validation of a disease-specific measure of health-related quality of life for children with cystic fibrosis. J. Pediatr. Psychol. 28, 535-545 (2003).
The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a disease-specific health-related quality of life (HRQOL) measure for children, adolescents and adults with cystic fibrosis (CF). It is a profile measure of HRQOL with several different domains. It has undergone extensive reliability and validity testing.
The Cystic Fibrosis Questionnaire-Revised (CFQ-R) application calculates the score derived from the CFQ-R, on a 0-100 scale with higher scores indicating better HRQoL.
measure: Evolution of the composition of the bacterial intestinal microbiota
time frame: Change from Baseline measurement at 3 months
description: The composition of the bacterial intestinal microbiota will be assessed by High-throughput sequencing and phylogenetic allocation of the bacterial flora (on MiSeq, from Illumina®)
measure: Evolution of the composition of the fungal intestinal microbiota
time frame: Change from Baseline measurement at 3 months
description: The composition of the fungal intestinal microbiota will be assessed by high-throughput sequencing and phylogenetic allocation of the fungal flora (on MiSeq, from Illumina®)
measure: Evolution of the pulmonary inflammation, assessed by the dosage of calprotectin in the sputum
time frame: Change from Baseline measurement at 3 months
description: Evolution of the Pulmonary inflammation will be assessed by measurement of salivary calprotectin (µg / g) by an ELISA biological test between the initiation of treatment (D0) and 3 months of treatment with polyethylene glycol (M3)
arm group label: Polyethylene glycol treatment
arm group type: Experimental
description: Study participants will take a 3-month laxative treatment with polyethylene glycol for 3 months.
intervention type: Drug
intervention name: Treatment with polyethylene glycol (Macrogol 4000)
description: 3-month treatment with polyethylene glycol (Macrogol 4000), powder for oral solution, in 4g and 10g sachets. Dosage of 0.7 g/kg/day, with a maximum dose of 20 g/day.
arm group label: Polyethylene glycol treatment
criteria: 
gender: All
minimum age: 4 Years
maximum age: 17 Years
healthy volunteers: No
last name: Marie M MITTAINE, MD
role: Principal Investigator
affiliation: CHU de Toulouse - Hôpital des Enfants - Centre de Ressources et de Compétences de la Mucoviscidose (CRCM) pédiatrique
last name: Raphaël R ENAUD, MD
phone: 0556799824
email: raphael.enaud@chu-bordeaux.fr
last name: Aurore CAPELLI, PhD
phone: 0557820877
email: aurore.capelli@chu-bordeaux.fr
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Fibrosis
mesh term: Inflammation