xml: <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/NCT05987501</url>
    </required_header>
    <id_info>
      <org_study_id>2743</org_study_id>
      <nct_id>NCT05987501</nct_id>
    </id_info>
    <brief_title>Multimodal Ultrasound in Inflammatory Bowel Diseases</brief_title>
    <acronym>CELESTIAL</acronym>
    <official_title>Prospective Study to Evaluate the Role of Contrast-enhanced Ultrasound (CEUS) and Elastography in Predicting Clinical and Endoscopic Remission (Deep Remission) in Inflammatory Bowel Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The role of intestinal ultrasound in treatment monitoring has recently gained increasing&#xD;
        interest thanks to its non-invasiveness, cost-effectiveness and largely availability.&#xD;
        Moreover, new ultrasonographic tools, particularly dynamic contrast-enhanced ultrasound&#xD;
        (D-CEUS) and shear wave elastography (SWE) can provide further useful information, such as a&#xD;
        quantitative estimation of bowel intramural microvacularization and tissue stiffness.&#xD;
  &#xD;
        Aim of this study is to evaluate the role of D-CEUS and SWE in predicting deep remission at&#xD;
        12 months from treatment induction in IBD.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background: Clinical remission is no more considered an appropriate therapeutic target for&#xD;
        Inflammatory Bowel Diseases (IBD) and other parameters such as endoscopic and transmural&#xD;
        remission are now recognized as prognostic factors (&quot;deep remission&quot;). Correctly monitoring&#xD;
        treatment response is crucial to rapidly adequate therapeutic algorithms avoiding&#xD;
        complications. The role of intestinal ultrasound in treatment monitoring has recently gained&#xD;
        increasing interest thanks to its non-invasiveness, cost-effectiveness and largely&#xD;
        availability. Moreover, new ultrasonographic tools, particularly dynamic contrast-enhanced&#xD;
        ultrasound (D-CEUS) and shear wave elastography (SWE) can provide further useful information,&#xD;
        such as a quantitative estimation of bowel intramural microvacularization and tissue&#xD;
        stiffness.&#xD;
  &#xD;
        Primary objective: to evaluate the role of D-CEUS and SWE in predicting deep remission at 12&#xD;
        months from treatment induction in IBD.&#xD;
  &#xD;
        Secondary objectives:&#xD;
  &#xD;
          -  To evaluate the relationship between clinical activity and CEUS/elastography parameters&#xD;
  &#xD;
          -  To evaluate the relationship between endoscopic activity and CEUS/elastography&#xD;
             parameters&#xD;
  &#xD;
          -  To evaluate the relationship between inflammation indices and CEUS/elastography&#xD;
  &#xD;
        Exploratory aims:&#xD;
  &#xD;
          -  To evaluate the relationship between CEUS/elastography parameters and serum biomarkers&#xD;
             of fibrosis&#xD;
  &#xD;
          -  To evaluate the relationship between CEUS/elastography parameters and faecal microbiota&#xD;
             in a subset of patients Study design: Prospective, interventional, single-center study.&#xD;
             Methods: 50 consecutive patients with Crohn's disease or Ulcerative Colitis needing to&#xD;
             begin biologic treatment according to international guidelines and with an affected&#xD;
             intestinal segment detectable in B-mode ultrasound will be enrolled in the Unit of&#xD;
             Internal Medicine and Gastroenterology of the Policlinico Gemelli. Exclusion criteria&#xD;
             will be induction of biologic therapy in prophylaxis after surgery in Crohn's disease,&#xD;
             lack of visualization of affected intestinal tract (eg. obesity), diagnosis of&#xD;
             undetermined colitis, hearth failure, known allergy to ultrasound contrast agents,&#xD;
             pregnancy and lactation. Colonoscopies, blood tests and ultrasound evaluations (B-mode&#xD;
             ultrasound, elastography and CEUS) will be performed as per normal clinical practice.&#xD;
             Data obtained from these procedures will be recorded and analyzed specifically for the&#xD;
             study. The only study-specific procedures are the collection of fecal samples for&#xD;
             microbiota evaluation, urine samples for metabolomics evaluation and an additional blood&#xD;
             sample for evaluation of fibrosis biomarkers, both collected at the time of recruitment.&#xD;
             The additional blood sample will be taken from the same peripheral venous access route&#xD;
             used for blood sampling in normal clinical practice. Ileal elastography and CEUS will be&#xD;
             performed before starting treatment and after 2/3, 8 and 16 weeks, 6 months, 12 months,&#xD;
             24 months and 36 months. If indicated by clinical assessment, some patients will be&#xD;
             re-evaluated after 3 weeks. Clinical assessment will include Harvey-Bradshaw index or&#xD;
             Mayo score, blood cell count, CRP and ESR, as per clinical practice. An additional blood&#xD;
             sampling will be done for fibrosis biomarker evaluation. In particular, we will do&#xD;
             multiple analysis (Bio-Plex, Biorad ) for IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8,&#xD;
             IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, basic FGF, G-CSF, GM-CSF, IFN-g,&#xD;
             IP-10, MCP-1, MIP-1a, PDGF-bb, MIP-1b, RANTES, TNF-a, VEGF, TL -1a, TGF-b, IL-33, ST2.&#xD;
             Data about the clinical outcome (i.e. surgery, hospitalizations, need for steroids…) and&#xD;
             biomarkers of fibrosis will be collected up to 36 months after the start of the study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">December 1, 2019</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">June 2024</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>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>predicting treatment response</measure>
      <time_frame>12 months after treatment induction</time_frame>
      <description>to quantify peak enhancement intensity in Arbitray Units AU (measured by analysing D-CEUS time-intensity curves) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>predicting treatment response</measure>
      <time_frame>12 months after treatment induction</time_frame>
      <description>to quantify the other D-CEUS parameters (measured by analysing D-CEUS time-intensity curves) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>predicting treatment response</measure>
      <time_frame>12 months after treatment induction</time_frame>
      <description>to quantify mean intestinal loop stiffness (measured by shear wave elastography) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Inflammatory Bowel Diseases</condition>
    <arm_group>
      <arm_group_label>Patients</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>patients with Crohn's disease or Ulcerative Colitis needing to begin biologic treatment</description>
    </arm_group>
    <intervention>
      <intervention_type>Diagnostic Test</intervention_type>
      <intervention_name>Multimodal ultrasound</intervention_name>
      <description>Contrast enhanced ultrasound and shear wave elastography on target intestinal loop are perfomed before and at different timepoints after treatment induction</description>
      <arm_group_label>Patients</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  written informed consent&#xD;
  &#xD;
            -  diagnosis of Crohn's disease or Ulcerative Colitis&#xD;
  &#xD;
            -  indication to start biologic treatment according to international guidelines&#xD;
  &#xD;
            -  affected intestinal segment detectable in B-mode ultrasound&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  induction of biologic therapy in prophylaxis after surgery in Crohn's disease&#xD;
  &#xD;
            -  lack of visualization of affected intestinal tract (eg. obesity)&#xD;
  &#xD;
            -  diagnosis of undetermined colitis&#xD;
  &#xD;
            -  hearth failure&#xD;
  &#xD;
            -  known allergy to ultrasound contrast agents&#xD;
  &#xD;
            -  pregnancy&#xD;
  &#xD;
            -  lactation&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Maria Assunta Zocco</last_name>
      <phone>00393470597805</phone>
      <email>mariaassunta.zocco@policlinicogemelli.it</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fondazione Policlinico Gemelli IRCCS</name>
        <address>
          <city>Roma</city>
          <zip>00168</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>MARIA ASSUNTA ZOCCO, PhD</last_name>
        <phone>00393470597805</phone>
      </contact>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>March 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fondazione Policlinico Universitario Agostino Gemelli IRCCS</investigator_affiliation>
      <investigator_full_name>Zocco Maria Assunta</investigator_full_name>
      <investigator_title>Prof</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Intestinal Diseases</mesh_term>
      <mesh_term>Inflammatory Bowel Diseases</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05987501
  org study id: 2743
  nct id: NCT05987501
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The role of intestinal ultrasound in treatment monitoring has recently gained increasing
        interest thanks to its non-invasiveness, cost-effectiveness and largely availability.
        Moreover, new ultrasonographic tools, particularly dynamic contrast-enhanced ultrasound
        (D-CEUS) and shear wave elastography (SWE) can provide further useful information, such as a
        quantitative estimation of bowel intramural microvacularization and tissue stiffness.
  
        Aim of this study is to evaluate the role of D-CEUS and SWE in predicting deep remission at
        12 months from treatment induction in IBD.
  Background: Clinical remission is no more considered an appropriate therapeutic target for
        Inflammatory Bowel Diseases (IBD) and other parameters such as endoscopic and transmural
        remission are now recognized as prognostic factors ("deep remission"). Correctly monitoring
        treatment response is crucial to rapidly adequate therapeutic algorithms avoiding
        complications. The role of intestinal ultrasound in treatment monitoring has recently gained
        increasing interest thanks to its non-invasiveness, cost-effectiveness and largely
        availability. Moreover, new ultrasonographic tools, particularly dynamic contrast-enhanced
        ultrasound (D-CEUS) and shear wave elastography (SWE) can provide further useful information,
        such as a quantitative estimation of bowel intramural microvacularization and tissue
        stiffness.
  
        Primary objective: to evaluate the role of D-CEUS and SWE in predicting deep remission at 12
        months from treatment induction in IBD.
  
        Secondary objectives:
  
          -  To evaluate the relationship between clinical activity and CEUS/elastography parameters
  
          -  To evaluate the relationship between endoscopic activity and CEUS/elastography
             parameters
  
          -  To evaluate the relationship between inflammation indices and CEUS/elastography
  
        Exploratory aims:
  
          -  To evaluate the relationship between CEUS/elastography parameters and serum biomarkers
             of fibrosis
  
          -  To evaluate the relationship between CEUS/elastography parameters and faecal microbiota
             in a subset of patients Study design: Prospective, interventional, single-center study.
             Methods: 50 consecutive patients with Crohn's disease or Ulcerative Colitis needing to
             begin biologic treatment according to international guidelines and with an affected
             intestinal segment detectable in B-mode ultrasound will be enrolled in the Unit of
             Internal Medicine and Gastroenterology of the Policlinico Gemelli. Exclusion criteria
             will be induction of biologic therapy in prophylaxis after surgery in Crohn's disease,
             lack of visualization of affected intestinal tract (eg. obesity), diagnosis of
             undetermined colitis, hearth failure, known allergy to ultrasound contrast agents,
             pregnancy and lactation. Colonoscopies, blood tests and ultrasound evaluations (B-mode
             ultrasound, elastography and CEUS) will be performed as per normal clinical practice.
             Data obtained from these procedures will be recorded and analyzed specifically for the
             study. The only study-specific procedures are the collection of fecal samples for
             microbiota evaluation, urine samples for metabolomics evaluation and an additional blood
             sample for evaluation of fibrosis biomarkers, both collected at the time of recruitment.
             The additional blood sample will be taken from the same peripheral venous access route
             used for blood sampling in normal clinical practice. Ileal elastography and CEUS will be
             performed before starting treatment and after 2/3, 8 and 16 weeks, 6 months, 12 months,
             24 months and 36 months. If indicated by clinical assessment, some patients will be
             re-evaluated after 3 weeks. Clinical assessment will include Harvey-Bradshaw index or
             Mayo score, blood cell count, CRP and ESR, as per clinical practice. An additional blood
             sampling will be done for fibrosis biomarker evaluation. In particular, we will do
             multiple analysis (Bio-Plex, Biorad ) for IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8,
             IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, Eotaxin, basic FGF, G-CSF, GM-CSF, IFN-g,
             IP-10, MCP-1, MIP-1a, PDGF-bb, MIP-1b, RANTES, TNF-a, VEGF, TL -1a, TGF-b, IL-33, ST2.
             Data about the clinical outcome (i.e. surgery, hospitalizations, need for steroids…) and
             biomarkers of fibrosis will be collected up to 36 months after the start of the study.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: predicting treatment response
  time frame: 12 months after treatment induction
  description: to quantify peak enhancement intensity in Arbitray Units AU (measured by analysing D-CEUS time-intensity curves) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)
  measure: predicting treatment response
  time frame: 12 months after treatment induction
  description: to quantify the other D-CEUS parameters (measured by analysing D-CEUS time-intensity curves) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)
  measure: predicting treatment response
  time frame: 12 months after treatment induction
  description: to quantify mean intestinal loop stiffness (measured by shear wave elastography) in patients with inflammatory bowel diseases undergoing biological treatment, stratified according to 12-months response to treatment (responders vs non-responders)
  arm group label: Patients
  arm group type: Experimental
  description: patients with Crohn's disease or Ulcerative Colitis needing to begin biologic treatment
  intervention type: Diagnostic Test
  intervention name: Multimodal ultrasound
  description: Contrast enhanced ultrasound and shear wave elastography on target intestinal loop are perfomed before and at different timepoints after treatment induction
  arm group label: Patients
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Maria Assunta Zocco
  phone: 00393470597805
  email: mariaassunta.zocco@policlinicogemelli.it
  facility: 
  status: Recruiting
  contact: 
  country: Italy
  responsible party type: Principal Investigator
  investigator affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  investigator full name: Zocco Maria Assunta
  investigator title: Prof
  mesh term: Intestinal Diseases
  mesh term: Inflammatory Bowel Diseases