<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/NCT02197780</url>
  </required_header>
  <id_info>
    <org_study_id>UMCG-2013N636</org_study_id>
    <nct_id>NCT02197780</nct_id>
  </id_info>
  <brief_title>Head-to-head Comparison of Two Fecal Biomarkers to Screen Children for IBD</brief_title>
  <acronym>CACATU</acronym>
  <official_title>Calprotectin or Calgranulin C-test Before Undergoing Endoscopy: a Prospective Diagnostic Accuracy Study Comparing Two Fecal Biomarkers for Pediatric IBD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Cisbio Bioassays</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Medical Center Groningen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      RATIONALE:&#xD;
&#xD;
      A substantial proportion of children and teenagers with suspected inflammatory bowel disease&#xD;
      (IBD) referred for endoscopy do not have the disease. The investigators designed a clinical&#xD;
      decision rule that included a calprotectin stool test to discern which patients require&#xD;
      further investigations. The accuracy of this diagnostic strategy is 88.5% with a low risk of&#xD;
      missing IBD cases. Although the number of negative endoscopies was reduced after introduction&#xD;
      of this strategy, still 22% of the referred children and teenagers underwent an unnecessary&#xD;
      invasive test. S100A12 (calgranulin C) is a cytoplasmic protein secreted exclusively by&#xD;
      activated neutrophils and this stool marker may be more IBD-specific than calprotectin.&#xD;
&#xD;
      OBJECTIVE:&#xD;
&#xD;
      To determine whether the specificity of S100A12 is superior to the specificity of&#xD;
      calprotectin without sacrificing sensitivity&#xD;
&#xD;
      HYPOTHESIS:&#xD;
&#xD;
      Inclusion of the calgranulin C stool test will improve the specificity of the&#xD;
      screening-strategy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      DESIGN:&#xD;
&#xD;
      A prospective diagnostic accuracy study in several outpatient clinics for general paediatrics&#xD;
      and several tertiary care hospitals in the Netherlands and Belgium.&#xD;
&#xD;
      STUDY POPULATION:&#xD;
&#xD;
      Eligible for inclusion are consecutive children and teenagers between 6 and 18 years who&#xD;
      consult their pediatrician and have gastro-intestinal symptoms suggestive of IBD.&#xD;
&#xD;
      INTERVENTION:&#xD;
&#xD;
      Patients will be managed according to a calprotectin-based-referral strategy. Those with an&#xD;
      elevated calprotectin level without colon pathogens are considered to have a high probability&#xD;
      of IBD and may require referral for endoscopy (the preferred reference standard). Patients&#xD;
      with confirmed gastrointestinal infection are advised to have their stools retested. Patients&#xD;
      with normal calprotectin levels are considered to have a low probability of IBD and will&#xD;
      therefore have a low change to be subjected to endoscopy. In these patients with low&#xD;
      probablity of IBD an alternative reference standard may be performed, being clinical&#xD;
      follow-up for 6 months. The decision for endoscopy or clinical follow up is up to the&#xD;
      clinician's discretion, based on the combination of all symptoms, physical examination, blood&#xD;
      results, fecal markers and colon pathogens.&#xD;
&#xD;
      Next to calprotectin, also S100A12 will be measured in all stool samples. We will perform a&#xD;
      post hoc scenario analysis to compare the test characteristics of both fecal markers.&#xD;
&#xD;
      OUTCOME MEASURES:&#xD;
&#xD;
      The primary outcome measure is the difference in specificity between FC and S100A12 among the&#xD;
      total number of non-IBD patients.&#xD;
&#xD;
      We adjusted our previously formulated outcome measure, being the proportion of patients with&#xD;
      non-inflammatory conditions among the total number of patient subjected to endoscopy, for two&#xD;
      reasons.&#xD;
&#xD;
        1. During an interim analysis in August 2016 the proportion of patients subjected to&#xD;
           endoscopy was lower as expected (34% instead 46%). To reach the required amount of&#xD;
           patients with the reference standard (endoscopy) we needed to extend the study for&#xD;
           several months.&#xD;
&#xD;
        2. Triggered by a recently published paper by Naaktgeboren et al in the BMJ, we realized&#xD;
           that our initial design would lead to biased results.&#xD;
&#xD;
      Secondary endpoints are the difference in sensitivity among the total number of patients with&#xD;
      IBD and the diagnostic accuracy characteristics (sensitivity, specificity, positive&#xD;
      predictive value, negative predictive value, area under the curve, best cut-off point) for&#xD;
      both markers individually. All diagnostic accuracy characteristics will be calculated with 1)&#xD;
      a pre-specified cut-off value based on literature, 2) the best cut-off point calculated with&#xD;
      the data from this trial.&#xD;
&#xD;
      POWER/DATA ANALYSIS:&#xD;
&#xD;
      At the start of our trial we defined a sample size calculation, based on the previously&#xD;
      described outcome measure including only patients with endoscopy. Based on a previous cohort&#xD;
      study we expected that 46% of the recruited patients would undergo endoscopy. Using a sample&#xD;
      size calculation based on independent samples calculated with a Fisher's exact test, we&#xD;
      calculated that with 154 patients subjected to endoscopy the study would have 80% power to&#xD;
      detect a 50% relative reduction of the primary outcome from 22% false positives with FC to&#xD;
      11% false positives with S100A12, at a one-sided alpha level of 0.05. The total number of&#xD;
      patients to be recruited for this diagnostic accuracy study was therefore calculated at 335.&#xD;
&#xD;
      In the slipstream of the adjustment of the primary outcome measure, we adjusted our sample&#xD;
      size. We now use McNemar's test for paired samples to compare the proportion of concordant&#xD;
      and discordant results between FC and S100A12 in all patients with the disease or without the&#xD;
      disease.&#xD;
&#xD;
      To calculate the new sample size we used a specificity of FC of 0.70, based on recent&#xD;
      individual patient data meta-analysis of Degraeuwe and we expected S100A12 would lead to 50%&#xD;
      relative improvement. A sample size of 130 subjects achieves 80% power to detect a difference&#xD;
      of 0,15 between the two diagnostic tests whose specificities are 0,70 and 0,85. This&#xD;
      procedure uses a two-sided McNemar test with a significance level of 0,05. The prevalence of&#xD;
      non-IBD in the population is 0,64. The proportion of discordant pairs is 0,23.&#xD;
&#xD;
      ETHICAL CONSIDERATIONS:&#xD;
&#xD;
      The Medical Ethical Committee of the University Medical Center in Groningen has granted&#xD;
      exemption from WMO-approval, as it involves the collection of data generated by routine&#xD;
      medical care. After measurement of calprotectin levels and testing for microbial gut&#xD;
      pathogens the residual material will be used for the measurement of calgranulin C levels.&#xD;
      When patients and their parents give permission, residual feces will be stored for a maximum&#xD;
      period of 15 years for future diagnostic research.&#xD;
&#xD;
      TIME SCHEDULE:&#xD;
&#xD;
      Total running time is 30 months, including 6 months to complete the follow up and 2 months&#xD;
      for analysis and reporting.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">April 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>6 Months</target_duration>
  <primary_outcome>
    <measure>The difference in specificity between FC and S100A12 among the total number of non-IBD patients.</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The difference in sensitivity between FC and S100A12 among the total number of IBD patients.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diagnostic test accuracy characteristics for both FC and S100A12</measure>
    <time_frame>6 months</time_frame>
    <description>Calculate sensitivity, specificity, positive predictive value, negative predictive value, area under ROC-curve, best cut-off point. The sensitivity, specificity, positive predictive value and negative predictive value will be presented with 1) a pre-specified cutoff value based on literature and 2) with the best cut-off points from this trial</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Scenario analysis with the test accuracy for a combination of FC and S100A12 in (sub)selection of patients.</measure>
    <time_frame>6 months</time_frame>
    <description>Scenario analysis with presentation of the number of true- and false positives and true- and false negatives for 1) only FC screening, 2) only S100A12 screening, 3) combination of FC and S100A12 screening, 4) combination of FC and S100A12 in sub-selection of patients with indeterminate result.</description>
  </other_outcome>
  <enrollment type="Actual">355</enrollment>
  <condition>Abdominal Pain</condition>
  <condition>Rectal Bloodloss</condition>
  <condition>Diarrhea</condition>
  <condition>Inflammatory Bowel Disease</condition>
  <condition>Crohn's Disease</condition>
  <condition>Ulcerative Colitis</condition>
  <condition>Irritable Bowel Syndrome</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Feces&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Eligible for inclusion are consecutive children and teenagers who consult their&#xD;
        pediatrician and have gastro-intestinal symptoms suggestive of IBD. Participating centers&#xD;
        are located in the Northern and Southern region of the Netherlands and the Flemish-speaking&#xD;
        region of Belgium.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Eligible patients are those aged between 6 and 18 years with at least one of the following&#xD;
        criteria:&#xD;
&#xD;
          -  Persistent diarrhea (at least 4 wks)&#xD;
&#xD;
          -  Recurrent abdominal pain with diarrhea (at least 2 episodes in 6 months)&#xD;
&#xD;
          -  Rectal bloodloss&#xD;
&#xD;
          -  Peri-anal disease&#xD;
&#xD;
        OR at least two of the following criteria:&#xD;
&#xD;
          -  Involuntary weight loss&#xD;
&#xD;
          -  First degree family member with IBD&#xD;
&#xD;
          -  Anemia (HB &lt; -2 SD for age and gender)&#xD;
&#xD;
          -  Increased marker of inflammation (ESR &gt;20 mm/hour or CRP &gt;10 mg/L)&#xD;
&#xD;
          -  Extra-intestinal symptoms (erythema nodosum, arthritis, uveitis, thromboembolism,&#xD;
             aphtous ulcera)&#xD;
&#xD;
        We did not define any exclusion criteria.&#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>Patrick F van Rheenen, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sint Vincentiusziekenhuis</name>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Antwerpen</name>
      <address>
        <city>Antwerpen</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Gent</name>
      <address>
        <city>Gent</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZGT Almelo</name>
      <address>
        <city>Almelo</city>
        <zip>7609 PP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wilhelmina Ziekenhuis</name>
      <address>
        <city>Assen</city>
        <zip>9401 RK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Deventer Ziekenhuis</name>
      <address>
        <city>Deventer</city>
        <zip>7416 SE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Nij Smellinghe</name>
      <address>
        <city>Drachten</city>
        <zip>9292 NN</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scheper Ziekenhuis</name>
      <address>
        <city>Emmen</city>
        <zip>7824 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisch Spectrum Twente</name>
      <address>
        <city>Enschede</city>
        <zip>7513 ER</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Admiraal de Ruyter ziekenhuis</name>
      <address>
        <city>Goes</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center Groningen</name>
      <address>
        <city>Groningen</city>
        <zip>9700 RB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martini Ziekenhuis</name>
      <address>
        <city>Groningen</city>
        <zip>9728 NT</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tjongerschans</name>
      <address>
        <city>Heerenveen</city>
        <zip>8441 PW</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bethesda Hospital</name>
      <address>
        <city>Hoogeveen</city>
        <zip>7909 AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medisch Centrum Leeuwarden (MCL)</name>
      <address>
        <city>Leeuwarden</city>
        <zip>8934 AD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bravis ziekenhuis</name>
      <address>
        <city>Roosendaal</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Refaja Ziekenhuis</name>
      <address>
        <city>Stadskanaal</city>
        <zip>9501 HE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ommelander Ziekenhuis Groep</name>
      <address>
        <city>Winschoten</city>
        <zip>9671 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Isala Kliniek</name>
      <address>
        <city>Zwolle</city>
        <zip>8025 AB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>May 3, 2017</last_update_submitted>
  <last_update_submitted_qc>May 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>P.F. van Rheenen</investigator_full_name>
    <investigator_title>Pediatric Gastroenterologist</investigator_title>
  </responsible_party>
  <keyword>Diagnostic accuracy</keyword>
  <keyword>Fecal biomarker</keyword>
  <keyword>Clinical Decision Rule</keyword>
  <keyword>Cohort Study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
    <mesh_term>Abdominal Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02197780
org study id: UMCG-2013N636
nct id: NCT02197780
lead sponsor: 
collaborator: 
has dmc: No
RATIONALE:

      A substantial proportion of children and teenagers with suspected inflammatory bowel disease
      (IBD) referred for endoscopy do not have the disease. The investigators designed a clinical
      decision rule that included a calprotectin stool test to discern which patients require
      further investigations. The accuracy of this diagnostic strategy is 88.5% with a low risk of
      missing IBD cases. Although the number of negative endoscopies was reduced after introduction
      of this strategy, still 22% of the referred children and teenagers underwent an unnecessary
      invasive test. S100A12 (calgranulin C) is a cytoplasmic protein secreted exclusively by
      activated neutrophils and this stool marker may be more IBD-specific than calprotectin.

      OBJECTIVE:

      To determine whether the specificity of S100A12 is superior to the specificity of
      calprotectin without sacrificing sensitivity

      HYPOTHESIS:

      Inclusion of the calgranulin C stool test will improve the specificity of the
      screening-strategy.
DESIGN:

      A prospective diagnostic accuracy study in several outpatient clinics for general paediatrics
      and several tertiary care hospitals in the Netherlands and Belgium.

      STUDY POPULATION:

      Eligible for inclusion are consecutive children and teenagers between 6 and 18 years who
      consult their pediatrician and have gastro-intestinal symptoms suggestive of IBD.

      INTERVENTION:

      Patients will be managed according to a calprotectin-based-referral strategy. Those with an
      elevated calprotectin level without colon pathogens are considered to have a high probability
      of IBD and may require referral for endoscopy (the preferred reference standard). Patients
      with confirmed gastrointestinal infection are advised to have their stools retested. Patients
      with normal calprotectin levels are considered to have a low probability of IBD and will
      therefore have a low change to be subjected to endoscopy. In these patients with low
      probablity of IBD an alternative reference standard may be performed, being clinical
      follow-up for 6 months. The decision for endoscopy or clinical follow up is up to the
      clinician's discretion, based on the combination of all symptoms, physical examination, blood
      results, fecal markers and colon pathogens.

      Next to calprotectin, also S100A12 will be measured in all stool samples. We will perform a
      post hoc scenario analysis to compare the test characteristics of both fecal markers.

      OUTCOME MEASURES:

      The primary outcome measure is the difference in specificity between FC and S100A12 among the
      total number of non-IBD patients.

      We adjusted our previously formulated outcome measure, being the proportion of patients with
      non-inflammatory conditions among the total number of patient subjected to endoscopy, for two
      reasons.

        1. During an interim analysis in August 2016 the proportion of patients subjected to
           endoscopy was lower as expected (34% instead 46%). To reach the required amount of
           patients with the reference standard (endoscopy) we needed to extend the study for
           several months.

        2. Triggered by a recently published paper by Naaktgeboren et al in the BMJ, we realized
           that our initial design would lead to biased results.

      Secondary endpoints are the difference in sensitivity among the total number of patients with
      IBD and the diagnostic accuracy characteristics (sensitivity, specificity, positive
      predictive value, negative predictive value, area under the curve, best cut-off point) for
      both markers individually. All diagnostic accuracy characteristics will be calculated with 1)
      a pre-specified cut-off value based on literature, 2) the best cut-off point calculated with
      the data from this trial.

      POWER/DATA ANALYSIS:

      At the start of our trial we defined a sample size calculation, based on the previously
      described outcome measure including only patients with endoscopy. Based on a previous cohort
      study we expected that 46% of the recruited patients would undergo endoscopy. Using a sample
      size calculation based on independent samples calculated with a Fisher's exact test, we
      calculated that with 154 patients subjected to endoscopy the study would have 80% power to
      detect a 50% relative reduction of the primary outcome from 22% false positives with FC to
      11% false positives with S100A12, at a one-sided alpha level of 0.05. The total number of
      patients to be recruited for this diagnostic accuracy study was therefore calculated at 335.

      In the slipstream of the adjustment of the primary outcome measure, we adjusted our sample
      size. We now use McNemar's test for paired samples to compare the proportion of concordant
      and discordant results between FC and S100A12 in all patients with the disease or without the
      disease.

      To calculate the new sample size we used a specificity of FC of 0.70, based on recent
      individual patient data meta-analysis of Degraeuwe and we expected S100A12 would lead to 50%
      relative improvement. A sample size of 130 subjects achieves 80% power to detect a difference
      of 0,15 between the two diagnostic tests whose specificities are 0,70 and 0,85. This
      procedure uses a two-sided McNemar test with a significance level of 0,05. The prevalence of
      non-IBD in the population is 0,64. The proportion of discordant pairs is 0,23.

      ETHICAL CONSIDERATIONS:

      The Medical Ethical Committee of the University Medical Center in Groningen has granted
      exemption from WMO-approval, as it involves the collection of data generated by routine
      medical care. After measurement of calprotectin levels and testing for microbial gut
      pathogens the residual material will be used for the measurement of calgranulin C levels.
      When patients and their parents give permission, residual feces will be stored for a maximum
      period of 15 years for future diagnostic research.

      TIME SCHEDULE:

      Total running time is 30 months, including 6 months to complete the follow up and 2 months
      for analysis and reporting.
observational model: Cohort
time perspective: Prospective
measure: The difference in specificity between FC and S100A12 among the total number of non-IBD patients.
time frame: 6 months
measure: The difference in sensitivity between FC and S100A12 among the total number of IBD patients.
time frame: 6 months
measure: Diagnostic test accuracy characteristics for both FC and S100A12
time frame: 6 months
description: Calculate sensitivity, specificity, positive predictive value, negative predictive value, area under ROC-curve, best cut-off point. The sensitivity, specificity, positive predictive value and negative predictive value will be presented with 1) a pre-specified cutoff value based on literature and 2) with the best cut-off points from this trial
measure: Scenario analysis with the test accuracy for a combination of FC and S100A12 in (sub)selection of patients.
time frame: 6 months
description: Scenario analysis with presentation of the number of true- and false positives and true- and false negatives for 1) only FC screening, 2) only S100A12 screening, 3) combination of FC and S100A12 screening, 4) combination of FC and S100A12 in sub-selection of patients with indeterminate result.
Feces
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: 18 Years
healthy volunteers: No
last name: Patrick F van Rheenen, MD PhD
role: Principal Investigator
affiliation: University Medical Center Groningen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: P.F. van Rheenen
investigator title: Pediatric Gastroenterologist
mesh term: Crohn Disease
mesh term: Inflammatory Bowel Diseases
mesh term: Irritable Bowel Syndrome
mesh term: Diarrhea
mesh term: Abdominal Pain
sharing ipd: Undecided