<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/NCT02201693</url>
  </required_header>
  <id_info>
    <org_study_id>P130302</org_study_id>
    <secondary_id>2013-A01473-42</secondary_id>
    <nct_id>NCT02201693</nct_id>
  </id_info>
  <brief_title>Cyclic Exclusive Enteral Nutrition as Maintenance Therapy for Pediatric Crohn's Disease</brief_title>
  <acronym>CD-HOPE</acronym>
  <official_title>Randomised Trial Comparing 12 Months of Cyclic Enteral Nutrition to Supplementary Enteral Nutrition as Maintenance Therapy for Pediatric Crohn's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GETAID Pediatric</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to compare the rate of first relapse at 12 months between&#xD;
      maintenance therapy with cyclic exclusive enteral nutrition (EEN) (at least 100% daily&#xD;
      calories) and maintenance therapy with supplementary enteral nutritional support (25% daily&#xD;
      calories).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Enteral nutrition (EN) is a highly efficacious treatment option for Crohn's disease (CD). In&#xD;
      children, exclusive EN is considered first choice therapy to induce remission in pediatric&#xD;
      CD, as highlighted in the recent ESPGHAN-ECCO guidelines. Several meta-analyses showed that&#xD;
      the anti-inflammatory potential of EEN is comparable to the effects of steroids. In addition,&#xD;
      children with CD often have marked growth retardation and EEN is one of the most efficacious&#xD;
      treatment options to induce catch-up growth in these patients. There is convincing data&#xD;
      indicating that EN is highly efficacious when given on an exclusive basis, while the use of&#xD;
      partial EN is markedly less effective to induce remission in active Crohn's disease as&#xD;
      compared to exclusive EN. Recently, it was suggested that exclusive EN has a dominant effect&#xD;
      on the intestinal microbiota, which contributes to the induction of remission. There exists&#xD;
      several strategies to maintain remission in children with CD, but there is no clear consensus&#xD;
      on which maintenance treatment to follow. There are some indicators to believe that enteral&#xD;
      nutritional therapy might play also a significant role as maintenance therapy for CD. Given&#xD;
      the fact that many centers use a top-down approach with the introduction of immunosuppressors&#xD;
      and/or biologics at/or shortly after diagnosis, the investigators wanted to test the&#xD;
      possibility of a treatment option to efficiently maintain remission with less (or no) side&#xD;
      effects based on enteral nutrition to avoid the early use of immunosuppressors.&#xD;
&#xD;
      It's a French multicenter, prospective, randomized study with PROBE (prospective randomized&#xD;
      open blind end-point) evaluation. Randomization will be performed in a blinded and&#xD;
      centralized manner, allocating patients to one of the two treatment groups :&#xD;
&#xD;
        -  ARM A : Cyclic exclusive MODULEN IBD for 2 weeks every 8 weeks&#xD;
&#xD;
        -  ARM B: MODULEN IBD supplementation (25% of caloric requirements) alone&#xD;
&#xD;
      A Physician not involved in the study design and blinded to the treatment arm will perform&#xD;
      the evaluation of the patients during each study visit.&#xD;
&#xD;
      A total of four visits (including final visit) are scheduled for this trial over a period of&#xD;
      12 months at a rhythm of every three months (+/- 2 weeks) for all patients. The study visit&#xD;
      will happen during scheduled routine visits, necessary for the routine care of CD patients.&#xD;
      Each visit comprises a routine clinical evaluation. The assessment of maintenance of&#xD;
      remission is particularly important (wPCDAI&lt;12.5 points), a routine lab analysis including&#xD;
      fecal calprotectin is required at each visit. In addition, all relevant medical or other&#xD;
      events will be recorded. Only for patients who participate in the annex studies an additional&#xD;
      stool sample (microbial analysis) is required. At M9 visit, follow-up endoscopy (M12+/-&#xD;
      6weeks) and entero-MRI (M12+/- 6 weeks) will be programmed as part of the routine&#xD;
      surveillance of patients on maintenance therapy, allowing to adjust treatment in the&#xD;
      following if necessary. Compliance to treatment will be monitored by recordings of daily&#xD;
      MODULEN IBD intake during 2 week periods on the E-system. A quality of life E-questionnaire&#xD;
      will be filled out one day prior to each visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 12, 2014</start_date>
  <completion_date type="Actual">October 2, 2019</completion_date>
  <primary_completion_date type="Actual">October 2, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The first relapse</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed with wPCDAI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical remission</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed with wPCDAI, CDAI, PGA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to the first relapse</measure>
    <time_frame>until month 12</time_frame>
    <description>Assessed with wPCDAI, CDAI, PGA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of wPCDAI,</measure>
    <time_frame>until month12</time_frame>
    <description>Assessed with wPCDAI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endoscopic remission</measure>
    <time_frame>month 12</time_frame>
    <description>CDEIS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transmural healing</measure>
    <time_frame>Month 12</time_frame>
    <description>MRI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Calprotectin</measure>
    <time_frame>until month12</time_frame>
    <description>Fecal sample</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life analysis</measure>
    <time_frame>Until Month 12</time_frame>
    <description>E-questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth pattern</measure>
    <time_frame>Until Month 12</time_frame>
    <description>Z-Score</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Cyclic exclusive MODULEN IBD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cyclic exclusive MODULEN IBD for 2 weeks every 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MODULEN IBD supplementation (25% of caloric requirements)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MODULEN IBD supplementation (25% of caloric requirements) alone A Physician not involved in the study design and blinded to the treatment arm will perform the evaluation of the patients during each study visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>MODULEN IBD</intervention_name>
    <description>2 week ON / 6 weeks OFF treatment every 8 weeks covering at least 100% of daily caloric requirement (approx. 2-2.5L/day).</description>
    <arm_group_label>Cyclic exclusive MODULEN IBD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>MODULEN IBD</intervention_name>
    <description>25% of daily caloric requirements, approx. 500mL/day</description>
    <arm_group_label>MODULEN IBD supplementation (25% of caloric requirements)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  6-18 years&#xD;
&#xD;
          -  Confirmed Crohn's disease (L1, L2, L3+/- L4a/b)&#xD;
&#xD;
          -  new-onset disease or acute relapse treated with enteral nutrition&#xD;
&#xD;
          -  responding to induction therapy with exclusive enteral nutrition with complete&#xD;
             clinical remission at inclusion visit (wPCDAI&lt;12.5)&#xD;
&#xD;
          -  completed cycle of induction therapy of at least 6 weeks (6-12 weeks)&#xD;
&#xD;
          -  biological treatment by Remicade has to be stopped at least 8 weeks prior to inclusion&#xD;
&#xD;
          -  &quot;wash out&quot; of corticosteroids, immunosuppressors and treatment by Humira of minimally&#xD;
             4 weeks prior to inclusion&#xD;
&#xD;
          -  5-ASA and derivates have to be stopped at least at screening visit&#xD;
&#xD;
          -  Antibiotics must be stopped at least 2 weeks prior to inclusion&#xD;
&#xD;
          -  Informed and signed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with B2 or B3 disease behavior (intestinal/colonic stenosis (including&#xD;
             ileo-caecal valve), intrabdominal abscess, fistulizing disease)&#xD;
&#xD;
          -  Patients not in remission on induction therapy (wPCDAI&gt;12.5)&#xD;
&#xD;
          -  Patients with isolated and severe perianal disease&#xD;
&#xD;
          -  Patients requiring surgical therapy at inclusion&#xD;
&#xD;
          -  Ongoing steroid medication&#xD;
&#xD;
          -  Ongoing immunosuppressor or biologics therapy&#xD;
&#xD;
          -  No informed consent&#xD;
&#xD;
          -  Currently participating or having participated in another interventional clinical&#xD;
             trial during the last 4 weeks prior to the beginning of this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Franck RUEMMELE, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Necker - Enfants Malades</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>April 13, 2021</last_update_submitted>
  <last_update_submitted_qc>April 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crohn's disease,</keyword>
  <keyword>pediatric GETAID (Therapeutic study group of inflammatory bowel diseases of the child),</keyword>
  <keyword>enteral nutrition,</keyword>
  <keyword>randomized multicenter study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</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/NCT02201693
org study id: P130302
secondary id: 2013-A01473-42
nct id: NCT02201693
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to compare the rate of first relapse at 12 months between
      maintenance therapy with cyclic exclusive enteral nutrition (EEN) (at least 100% daily
      calories) and maintenance therapy with supplementary enteral nutritional support (25% daily
      calories).
Enteral nutrition (EN) is a highly efficacious treatment option for Crohn's disease (CD). In
      children, exclusive EN is considered first choice therapy to induce remission in pediatric
      CD, as highlighted in the recent ESPGHAN-ECCO guidelines. Several meta-analyses showed that
      the anti-inflammatory potential of EEN is comparable to the effects of steroids. In addition,
      children with CD often have marked growth retardation and EEN is one of the most efficacious
      treatment options to induce catch-up growth in these patients. There is convincing data
      indicating that EN is highly efficacious when given on an exclusive basis, while the use of
      partial EN is markedly less effective to induce remission in active Crohn's disease as
      compared to exclusive EN. Recently, it was suggested that exclusive EN has a dominant effect
      on the intestinal microbiota, which contributes to the induction of remission. There exists
      several strategies to maintain remission in children with CD, but there is no clear consensus
      on which maintenance treatment to follow. There are some indicators to believe that enteral
      nutritional therapy might play also a significant role as maintenance therapy for CD. Given
      the fact that many centers use a top-down approach with the introduction of immunosuppressors
      and/or biologics at/or shortly after diagnosis, the investigators wanted to test the
      possibility of a treatment option to efficiently maintain remission with less (or no) side
      effects based on enteral nutrition to avoid the early use of immunosuppressors.

      It's a French multicenter, prospective, randomized study with PROBE (prospective randomized
      open blind end-point) evaluation. Randomization will be performed in a blinded and
      centralized manner, allocating patients to one of the two treatment groups :

        -  ARM A : Cyclic exclusive MODULEN IBD for 2 weeks every 8 weeks

        -  ARM B: MODULEN IBD supplementation (25% of caloric requirements) alone

      A Physician not involved in the study design and blinded to the treatment arm will perform
      the evaluation of the patients during each study visit.

      A total of four visits (including final visit) are scheduled for this trial over a period of
      12 months at a rhythm of every three months (+/- 2 weeks) for all patients. The study visit
      will happen during scheduled routine visits, necessary for the routine care of CD patients.
      Each visit comprises a routine clinical evaluation. The assessment of maintenance of
      remission is particularly important (wPCDAI<12.5 points), a routine lab analysis including
      fecal calprotectin is required at each visit. In addition, all relevant medical or other
      events will be recorded. Only for patients who participate in the annex studies an additional
      stool sample (microbial analysis) is required. At M9 visit, follow-up endoscopy (M12+/-
      6weeks) and entero-MRI (M12+/- 6 weeks) will be programmed as part of the routine
      surveillance of patients on maintenance therapy, allowing to adjust treatment in the
      following if necessary. Compliance to treatment will be monitored by recordings of daily
      MODULEN IBD intake during 2 week periods on the E-system. A quality of life E-questionnaire
      will be filled out one day prior to each visit.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The first relapse
time frame: 12 months
description: Assessed with wPCDAI
measure: Clinical remission
time frame: 12 months
description: Assessed with wPCDAI, CDAI, PGA
measure: Time to the first relapse
time frame: until month 12
description: Assessed with wPCDAI, CDAI, PGA
measure: Variation of wPCDAI,
time frame: until month12
description: Assessed with wPCDAI
measure: Endoscopic remission
time frame: month 12
description: CDEIS
measure: Transmural healing
time frame: Month 12
description: MRI
measure: Calprotectin
time frame: until month12
description: Fecal sample
measure: Quality of life analysis
time frame: Until Month 12
description: E-questionnaire
measure: Growth pattern
time frame: Until Month 12
description: Z-Score
arm group label: Cyclic exclusive MODULEN IBD
arm group type: Experimental
description: Cyclic exclusive MODULEN IBD for 2 weeks every 8 weeks
arm group label: MODULEN IBD supplementation (25% of caloric requirements)
arm group type: Experimental
description: MODULEN IBD supplementation (25% of caloric requirements) alone A Physician not involved in the study design and blinded to the treatment arm will perform the evaluation of the patients during each study visit.
intervention type: Dietary Supplement
intervention name: MODULEN IBD
description: 2 week ON / 6 weeks OFF treatment every 8 weeks covering at least 100% of daily caloric requirement (approx. 2-2.5L/day).
arm group label: Cyclic exclusive MODULEN IBD
intervention type: Dietary Supplement
intervention name: MODULEN IBD
description: 25% of daily caloric requirements, approx. 500mL/day
arm group label: MODULEN IBD supplementation (25% of caloric requirements)
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
last name: Franck RUEMMELE, MD, PhD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Crohn Disease
sharing ipd: No