<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/NCT02231814</url>
  </required_header>
  <id_info>
    <org_study_id>0105-14</org_study_id>
    <nct_id>NCT02231814</nct_id>
  </id_info>
  <brief_title>The Crohn's Disease Exclusion Diet With Partial Enteral Nutrition or Alone in Adult Patients With Crohn's Disease</brief_title>
  <acronym>CDED-AD</acronym>
  <official_title>Dietary Therapy Using the Crohn's Disease Exclusion Diet (CDED) With Partial Enteral Nutrition or Alone for Induction and Maintenance of Remission in in Adults With Mild to Moderate Crohn's Disease- A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prof. Arie Levine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wolfson Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate a novel diet for adult crohn's disease patients (The Crohn's Disease&#xD;
      Exclusion Diet - CDED). Half of the patients in this study will receive the CDED alone while&#xD;
      the other half will receive the CDED and a liquid diet formula, for 24 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Environmental factors, the microbiome (bacteria in our gut) and innate immunity all play a&#xD;
      role in the pathogenesis of Crohn's disease .Exclusive enteral nutrition (EEN) was found to&#xD;
      be effective for inducing remission in active pediatric Crohn's disease, while Partial&#xD;
      Enteral Nutrition (PEN) with free diet was not; suggesting that the mechanism of EEN depends&#xD;
      on exclusion of dietary components. Dietary factors may play a role in the pathogenesis of&#xD;
      the disease, and maybe an important under-investigated therapeutic target.&#xD;
&#xD;
      &quot;The Crohn's Disease Exclusion Diet&quot; (CDED) is a palatable diet excluding components&#xD;
      suspected to interfere with the bacteria in our gut or impair immune mechanisms. Our group&#xD;
      previously evaluated 47 patients using the Crohn's disease Exclusion Diet + 50% Polymeric&#xD;
      formula for 6 weeks, and demonstrated a 78% response rate and 70% disease remission rate&#xD;
      using stringent criteria. This was accompanied by a highly significant reduction in markers&#xD;
      for inflammation (C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR)), and&#xD;
      normalization of CRP in 70% of those entering remission. Among these patients were 13 adults&#xD;
      aged 19-32, the remission rate in these 13 patients was 69%, similar to the pediatric data.&#xD;
      Importantly, 6/7 patients in this study who refused to drink formula and just used the diet&#xD;
      achieved remission, suggesting that the exclusion and not partial enteral nutrition are&#xD;
      responsible for the high remission rate. Our former study did not evaluate mucosal healing as&#xD;
      an end point, since performing colonoscopies after 6- 12 weeks of therapy is neither ethical&#xD;
      nor feasible in children.&#xD;
&#xD;
      At present, data about nutritional therapy and this new dietary approach have been generated&#xD;
      primarily in children, and this new diet has not been evaluated for early mucosal healing.&#xD;
      The objectives of this pilot study are to generate data in adults, evaluate the diet over a&#xD;
      longer period of time (24 weeks) and evaluate mucosal healing. The study is a prospective&#xD;
      open label randomized controlled pilot trial in adults, with mild to moderate Crohn's disease&#xD;
      who will receive the Crohn's Disease Exclusion Diet (CDED) for 24 weeks.&#xD;
&#xD;
      If effective, this could enable use of a feasible, safe intervention for induction and&#xD;
      maintenance of remission as a new therapy or as an adjunctive therapy with medical therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">December 2020</completion_date>
  <primary_completion_date type="Actual">December 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical remission defined as Harvey Bradshaw Index (HBI)&lt;5</measure>
    <time_frame>Week 6</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Steroid free remission between groups</measure>
    <time_frame>Week 6, 12 and 24.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucosal healing</measure>
    <time_frame>Week 24-26</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in mean C-Reactive Protein (CRP)</measure>
    <time_frame>Weeks 6, 12 and 24.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in mean fecal calprotectin</measure>
    <time_frame>Week 6, 12 and 24</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Crohn's Disease Exclusion Diet+Partial Enteral Nutrition (PEN): Crohns Disease Exclusion Diet + PEN</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Crohn's Disease Exclusion Diet alone with a calcium supplement</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Crohns Disease Exclusion Diet + PEN</intervention_name>
    <description>Patients will use the CDED for a 24 week period, coupled with 1000 m&quot;l of polymeric formula (1 Kcal/m&quot;L) for the first 6 weeks. For weeks 7 to 24 patients will use the CDED coupled with 600 ml formula and a calcium supplement. The CDED is divided into 3 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase.</description>
    <arm_group_label>Group 1</arm_group_label>
    <other_name>CDED + Liquid dietary formula</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Crohns Disease Exclusion Diet</intervention_name>
    <description>Crohn's Disease Exclusion Diet alone with a calcium supplement during the study (0-24). The CDED is divided into 3 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase.</description>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>CDED</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Informed consent&#xD;
&#xD;
          2. Established Crohn's disease&#xD;
&#xD;
          3. Aged 18-55&#xD;
&#xD;
          4. Duration of disease up to 5 years&#xD;
&#xD;
          5. Harvey Bradshaw Index 5 ≤( HBI) ≤15&#xD;
&#xD;
          6. Patients with uncomplicated disease involving the terminal ileum and or cecum&#xD;
&#xD;
          7. Patients who performed colonoscopy (or MR/CTEnterography with elevated&#xD;
             calprotectin&gt;200) demonstrating active disease in the previous 8 weeks&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Patients with severe Disease (HBI &gt; 15) or HBI&lt;5&#xD;
&#xD;
          2. Pregnancy,&#xD;
&#xD;
          3. Patients with active extraintestinal disease, current B2 (Fixed non inflammatory&#xD;
             stricture1 or small bowel obstruction) or B3 disease,&#xD;
&#xD;
          4. Patients who used immunomodulator &lt;8 weeks, or had dose changed in past 8 weeks,&#xD;
&#xD;
          5. Patients with current or past use of biologics, or use of systemic steroids2,&#xD;
&#xD;
          6. Patients with deep ulcers involving the colon distal to the splenic flexure on most&#xD;
             recent colonoscopy&#xD;
&#xD;
          7. Any proven current infection such as positive stool cultures or positive tests for&#xD;
             parasites or C. difficile. Stool tests are mandatory only if diarrhea is present.&#xD;
&#xD;
          8. Active Perianal disease ( clarification-fistula with discharge or abscess)&#xD;
&#xD;
          9. Patients who have undergone an intestinal resection&#xD;
&#xD;
         10. Patients with systemic disease including: type 2 diabetes, kidney failure, liver&#xD;
             failure, neurological disease, active heart disease and patients with active&#xD;
             autoimmune condition requiring medication3&#xD;
&#xD;
         11. Patients unwilling to consume any animal source protein (eggs, chicken or fish).&#xD;
&#xD;
        Comments:&#xD;
&#xD;
          1. Patients with ileo-cecal valve narrowing maybe included&#xD;
&#xD;
          2. Patients active despite budesonide may enter the trial if they are on 3 mg, and stop&#xD;
             budesonide within 14 days of commencement of the trial.&#xD;
&#xD;
          3. Patients with Celiac disease or Hashimoto Thyroiditis can be enrolled&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arie Levine, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wolfson Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Iris Dotan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tel Aviv Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Irit Hermesh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rambam Medical Center,Haifa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Haemek</name>
      <address>
        <city>Afula</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wolfson Medical Center</name>
      <address>
        <city>Holon</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rabin Medical Center</name>
      <address>
        <city>Petach Tikva</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tel Aviv Sourasky Medical Center</name>
      <address>
        <city>Tel Aviv</city>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <reference>
    <citation>Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease. Inflamm Bowel Dis. 2014 Aug;20(8):1353-60. doi: 10.1097/MIB.0000000000000110.</citation>
    <PMID>24983973</PMID>
  </reference>
  <reference>
    <citation>Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2.</citation>
    <PMID>34739863</PMID>
  </reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 27, 2014</study_first_submitted>
  <study_first_submitted_qc>September 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>May 29, 2022</last_update_submitted>
  <last_update_submitted_qc>May 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Wolfson Medical Center</investigator_affiliation>
    <investigator_full_name>Prof. Arie Levine</investigator_full_name>
    <investigator_title>Director, Pediatric Gastroenterology and Nutrition unit.</investigator_title>
  </responsible_party>
  <keyword>Crohn's disease</keyword>
  <keyword>Mild to moderate Crohn's Disease</keyword>
  <keyword>Diet</keyword>
  <keyword>Enteral Nutrition</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</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/NCT02231814
org study id: 0105-14
nct id: NCT02231814
lead sponsor: 
has dmc: No
This study will evaluate a novel diet for adult crohn's disease patients (The Crohn's Disease
      Exclusion Diet - CDED). Half of the patients in this study will receive the CDED alone while
      the other half will receive the CDED and a liquid diet formula, for 24 weeks.
Environmental factors, the microbiome (bacteria in our gut) and innate immunity all play a
      role in the pathogenesis of Crohn's disease .Exclusive enteral nutrition (EEN) was found to
      be effective for inducing remission in active pediatric Crohn's disease, while Partial
      Enteral Nutrition (PEN) with free diet was not; suggesting that the mechanism of EEN depends
      on exclusion of dietary components. Dietary factors may play a role in the pathogenesis of
      the disease, and maybe an important under-investigated therapeutic target.

      "The Crohn's Disease Exclusion Diet" (CDED) is a palatable diet excluding components
      suspected to interfere with the bacteria in our gut or impair immune mechanisms. Our group
      previously evaluated 47 patients using the Crohn's disease Exclusion Diet + 50% Polymeric
      formula for 6 weeks, and demonstrated a 78% response rate and 70% disease remission rate
      using stringent criteria. This was accompanied by a highly significant reduction in markers
      for inflammation (C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR)), and
      normalization of CRP in 70% of those entering remission. Among these patients were 13 adults
      aged 19-32, the remission rate in these 13 patients was 69%, similar to the pediatric data.
      Importantly, 6/7 patients in this study who refused to drink formula and just used the diet
      achieved remission, suggesting that the exclusion and not partial enteral nutrition are
      responsible for the high remission rate. Our former study did not evaluate mucosal healing as
      an end point, since performing colonoscopies after 6- 12 weeks of therapy is neither ethical
      nor feasible in children.

      At present, data about nutritional therapy and this new dietary approach have been generated
      primarily in children, and this new diet has not been evaluated for early mucosal healing.
      The objectives of this pilot study are to generate data in adults, evaluate the diet over a
      longer period of time (24 weeks) and evaluate mucosal healing. The study is a prospective
      open label randomized controlled pilot trial in adults, with mild to moderate Crohn's disease
      who will receive the Crohn's Disease Exclusion Diet (CDED) for 24 weeks.

      If effective, this could enable use of a feasible, safe intervention for induction and
      maintenance of remission as a new therapy or as an adjunctive therapy with medical therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical remission defined as Harvey Bradshaw Index (HBI)<5
time frame: Week 6
measure: Steroid free remission between groups
time frame: Week 6, 12 and 24.
measure: Mucosal healing
time frame: Week 24-26
measure: Changes in mean C-Reactive Protein (CRP)
time frame: Weeks 6, 12 and 24.
measure: Change in mean fecal calprotectin
time frame: Week 6, 12 and 24
arm group label: Group 1
arm group type: Experimental
description: Crohn's Disease Exclusion Diet+Partial Enteral Nutrition (PEN): Crohns Disease Exclusion Diet + PEN
arm group label: Group 2
arm group type: Experimental
description: Crohn's Disease Exclusion Diet alone with a calcium supplement
intervention type: Dietary Supplement
intervention name: Crohns Disease Exclusion Diet + PEN
description: Patients will use the CDED for a 24 week period, coupled with 1000 m"l of polymeric formula (1 Kcal/m"L) for the first 6 weeks. For weeks 7 to 24 patients will use the CDED coupled with 600 ml formula and a calcium supplement. The CDED is divided into 3 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase.
arm group label: Group 1
other name: CDED + Liquid dietary formula
intervention type: Other
intervention name: Crohns Disease Exclusion Diet
description: Crohn's Disease Exclusion Diet alone with a calcium supplement during the study (0-24). The CDED is divided into 3 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase.
arm group label: Group 2
other name: CDED
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Arie Levine, MD
role: Principal Investigator
affiliation: Wolfson Medical Center
last name: Iris Dotan, MD
role: Principal Investigator
affiliation: Tel Aviv Medical Center
last name: Irit Hermesh, MD
role: Principal Investigator
affiliation: Rambam Medical Center,Haifa
facility: 
facility: 
facility: 
facility: 
country: Israel
citation: Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease. Inflamm Bowel Dis. 2014 Aug;20(8):1353-60. doi: 10.1097/MIB.0000000000000110.
PMID: 24983973
citation: Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2.
PMID: 34739863
responsible party type: Sponsor-Investigator
investigator affiliation: Wolfson Medical Center
investigator full name: Prof. Arie Levine
investigator title: Director, Pediatric Gastroenterology and Nutrition unit.
mesh term: Crohn Disease