<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/NCT01666626</url>
  </required_header>
  <id_info>
    <org_study_id>HUM64431</org_study_id>
    <nct_id>NCT01666626</nct_id>
  </id_info>
  <brief_title>Ultrasound Stiffness Imaging in Crohn's Disease</brief_title>
  <official_title>Investigating Ultrasound Stiffness Imaging for Predicting Outcomes in Crohn's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Crohn's and Colitis Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether ultrasound-based assessment of intestinal&#xD;
      stiffness in patients with Crohn's disease predicts the effectiveness of medical therapy or&#xD;
      the need for surgical resection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Modern medical therapy in Crohn's disease, including immunomodulators and biologic compounds,&#xD;
      has revolutionized disease treatment. However, a significant portion of individuals will not&#xD;
      respond to medications, most often due to the development of intestinal fibrosis. Over the&#xD;
      course of Crohn's disease repeated episodes of inflammation and abnormal wound healing lead&#xD;
      to progressive intestinal fibrosis, strictures, and bowel obstruction. While inflammatory&#xD;
      Crohn's disease often responds to medical therapy, predominantly fibrostenotic intestinal&#xD;
      disease is unresponsive and requires surgery. Our inability to accurately distinguish&#xD;
      intestinal inflammation from fibrosis frequently leads to empiric trials of steroids and&#xD;
      immunosuppressive therapies. This often proves futile, delays inevitable surgery, and&#xD;
      unnecessarily exposes the patient to medication-related risks for months and sometimes years.&#xD;
      At present there are no available means to distinguish medically responsive inflammatory&#xD;
      disease from predominately fibrotic intestinal disease. The unmet need in this field is an&#xD;
      accurate diagnostic technology to determine which patients will benefit from&#xD;
      anti-inflammatory therapy, and which patients should go directly to surgery. Non-invasive&#xD;
      ultrasound stiffness imaging (USI) may be a surrogate marker of underlying bowel wall&#xD;
      fibrosis that aids in predicting if Crohn's disease will be responsive to medical therapy.&#xD;
&#xD;
      Two USI methods have recently been developed: Ultrasound elasticity imaging (UEI) uses 2D&#xD;
      speckle-tracking to measure tissue strain, a surrogate of fibrosis. The second, shear wave&#xD;
      imaging (SWI), is a commercially available technology that measures the speed of ultrasonic&#xD;
      shear waves through tissue. Shear waves travel more rapidly through stiff tissue. The central&#xD;
      hypothesis of this proposal is that ultrasound stiffness imaging (USI) quantitatively&#xD;
      distinguishes predominately inflammatory from fibrotic bowel wall thickening, and therefore&#xD;
      is predictive of the likelihood of response to medical therapy or the need for surgery.&#xD;
&#xD;
      We plan to objectively test our central hypothesis and attain the objective of this&#xD;
      application by pursuing the following three specific aims:&#xD;
&#xD;
      Specific Aim 1 (SA-1): Determine if USI stiffness measurements of intestinal strictures in&#xD;
      Crohn's patients admitted with small bowel obstruction predicts response or failure of&#xD;
      medical therapy based on CDAI and objective inflammatory biomarkers during index&#xD;
      hospitalization and at 90 day follow-up.&#xD;
&#xD;
      Inpatient Inclusion Criteria:&#xD;
&#xD;
        -  Subjects must be 18 years of age or older&#xD;
&#xD;
        -  Previous diagnosis of Crohn's disease with imaging demonstrating involvement of the&#xD;
           ileum&#xD;
&#xD;
        -  Hospital admission imaging demonstrating small bowel dilation (to &gt; 3.5 cm)&#xD;
&#xD;
        -  CDAI score of &gt;220.&#xD;
&#xD;
      Inpatient Exclusion Criteria:&#xD;
&#xD;
        -  Active Clostridium difficile colitis/enteritis&#xD;
&#xD;
        -  Presence of abdominal enterocutaneous fistulas in the ultrasound path.&#xD;
&#xD;
        -  Prior abdominal hernia repair with mesh placement in the ultrasound path.&#xD;
&#xD;
      Specific Aim 2 (SA-2): Determine if USI stiffness measurements of diseased ileum in Crohn's&#xD;
      outpatients starting Anti-Tumor Necrosis Factor-Alpha therapy predicts response to medical&#xD;
      therapy based on CDAI and objective inflammatory biomarkers.&#xD;
&#xD;
      Outpatient Inclusion Criteria&#xD;
&#xD;
        -  Crohn's patients age 18 and over starting anti-TNF therapy&#xD;
&#xD;
        -  CDAI score &gt; 220 to denote clinical disease activity.&#xD;
&#xD;
      Outpatient Exclusion Criteria:&#xD;
&#xD;
        -  Active Clostridium difficile colitis/enteritis&#xD;
&#xD;
        -  Presence of abdominal enterocutaneous fistulas in the ultrasound path&#xD;
&#xD;
        -  Prior abdominal hernia repair with mesh placement in the ultrasound path&#xD;
&#xD;
        -  Current use of prednisone or budesonide&#xD;
&#xD;
        -  Changing anti-TNF due to allergy (including a TNF-induced lupus-like arthritis).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 2015</completion_date>
  <primary_completion_date type="Actual">July 2015</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Change in CDAI Score Over 90 days from Hospital Admission</measure>
    <time_frame>CDAI Score measured over 90 days</time_frame>
    <description>CDAI score will be assessed at 3 time points:&#xD;
Hospital Admission Hospital Discharge 90-day follow-up</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Shear Wave Velocity</measure>
    <time_frame>Day 0,3,5,7 of Hospitalization</time_frame>
    <description>Ultrasound shear wave velocity measurements in bowel wall</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Need for Re-hospitalization or Surgery within 90 days of discharge</measure>
    <time_frame>90 days post discharge</time_frame>
    <description>Telephone follow up with subjects 90 days following index hospitalization to assess need for re-hospitalization or surgery</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">30</enrollment>
  <condition>Crohn's Disease</condition>
  <condition>Ultrasound</condition>
  <condition>Intestinal Fibrosis</condition>
  <condition>Shear Wave Imaging</condition>
  <condition>Acoustic Radiation Force Impulse</condition>
  <arm_group>
    <arm_group_label>Crohn's Inpatients</arm_group_label>
    <description>Crohn's Inpatients, with clinical small bowel obstruction All undergo ultrasound stiffness imaging (USI) of distal affected ileum.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Crohn's Outpatients</arm_group_label>
    <description>Crohn's Outpatients, starting anti-TNF therapy All undergo ultrasound stiffness imaging (USI) at week 0, 6, 14</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ultrasound stiffness imaging</intervention_name>
    <description>Subjects will undergo transabdominal ultrasound of the distal intestine. Distal intestine motion capture will be used for off-line stiffness assessment by two-dimensional speckle tracking. In addition, shear wave imaging will be used for real-time stiffness assessment.</description>
    <arm_group_label>Crohn's Inpatients</arm_group_label>
    <arm_group_label>Crohn's Outpatients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Adult patients with Crohn's disease, either:&#xD;
&#xD;
          -  hospitalized for small bowel obstruction, OR,&#xD;
&#xD;
          -  undergoing outpatient start of anti-tumor necrosis factor alpha&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  CDAI score &gt;220&#xD;
&#xD;
          -  if INPATIENT: admission for small bowel obstruction.&#xD;
&#xD;
          -  if OUTPATIENT: start of anti-tumor necrosis alpha therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active Clostridium difficile colitis/enteritis&#xD;
&#xD;
          -  Presence of abdominal enterocutaneous fistulas in the ultrasound path&#xD;
&#xD;
          -  Prior abdominal hernia repair with mesh placement in the ultrasound path&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ryan W Stidham, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Health System</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2015</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>July 29, 2015</last_update_submitted>
  <last_update_submitted_qc>July 29, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 30, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Ryan W. Stidham</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>crohn's disease</keyword>
  <keyword>ultrasound</keyword>
  <keyword>intestinal fibrosis</keyword>
  <keyword>shear wave imaging</keyword>
  <keyword>acoustic radiation force impulse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Fibrosis</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/NCT01666626
org study id: HUM64431
nct id: NCT01666626
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine whether ultrasound-based assessment of intestinal
      stiffness in patients with Crohn's disease predicts the effectiveness of medical therapy or
      the need for surgical resection.
Modern medical therapy in Crohn's disease, including immunomodulators and biologic compounds,
      has revolutionized disease treatment. However, a significant portion of individuals will not
      respond to medications, most often due to the development of intestinal fibrosis. Over the
      course of Crohn's disease repeated episodes of inflammation and abnormal wound healing lead
      to progressive intestinal fibrosis, strictures, and bowel obstruction. While inflammatory
      Crohn's disease often responds to medical therapy, predominantly fibrostenotic intestinal
      disease is unresponsive and requires surgery. Our inability to accurately distinguish
      intestinal inflammation from fibrosis frequently leads to empiric trials of steroids and
      immunosuppressive therapies. This often proves futile, delays inevitable surgery, and
      unnecessarily exposes the patient to medication-related risks for months and sometimes years.
      At present there are no available means to distinguish medically responsive inflammatory
      disease from predominately fibrotic intestinal disease. The unmet need in this field is an
      accurate diagnostic technology to determine which patients will benefit from
      anti-inflammatory therapy, and which patients should go directly to surgery. Non-invasive
      ultrasound stiffness imaging (USI) may be a surrogate marker of underlying bowel wall
      fibrosis that aids in predicting if Crohn's disease will be responsive to medical therapy.

      Two USI methods have recently been developed: Ultrasound elasticity imaging (UEI) uses 2D
      speckle-tracking to measure tissue strain, a surrogate of fibrosis. The second, shear wave
      imaging (SWI), is a commercially available technology that measures the speed of ultrasonic
      shear waves through tissue. Shear waves travel more rapidly through stiff tissue. The central
      hypothesis of this proposal is that ultrasound stiffness imaging (USI) quantitatively
      distinguishes predominately inflammatory from fibrotic bowel wall thickening, and therefore
      is predictive of the likelihood of response to medical therapy or the need for surgery.

      We plan to objectively test our central hypothesis and attain the objective of this
      application by pursuing the following three specific aims:

      Specific Aim 1 (SA-1): Determine if USI stiffness measurements of intestinal strictures in
      Crohn's patients admitted with small bowel obstruction predicts response or failure of
      medical therapy based on CDAI and objective inflammatory biomarkers during index
      hospitalization and at 90 day follow-up.

      Inpatient Inclusion Criteria:

        -  Subjects must be 18 years of age or older

        -  Previous diagnosis of Crohn's disease with imaging demonstrating involvement of the
           ileum

        -  Hospital admission imaging demonstrating small bowel dilation (to > 3.5 cm)

        -  CDAI score of >220.

      Inpatient Exclusion Criteria:

        -  Active Clostridium difficile colitis/enteritis

        -  Presence of abdominal enterocutaneous fistulas in the ultrasound path.

        -  Prior abdominal hernia repair with mesh placement in the ultrasound path.

      Specific Aim 2 (SA-2): Determine if USI stiffness measurements of diseased ileum in Crohn's
      outpatients starting Anti-Tumor Necrosis Factor-Alpha therapy predicts response to medical
      therapy based on CDAI and objective inflammatory biomarkers.

      Outpatient Inclusion Criteria

        -  Crohn's patients age 18 and over starting anti-TNF therapy

        -  CDAI score > 220 to denote clinical disease activity.

      Outpatient Exclusion Criteria:

        -  Active Clostridium difficile colitis/enteritis

        -  Presence of abdominal enterocutaneous fistulas in the ultrasound path

        -  Prior abdominal hernia repair with mesh placement in the ultrasound path

        -  Current use of prednisone or budesonide

        -  Changing anti-TNF due to allergy (including a TNF-induced lupus-like arthritis).
observational model: Cohort
time perspective: Prospective
measure: Change in CDAI Score Over 90 days from Hospital Admission
time frame: CDAI Score measured over 90 days
description: CDAI score will be assessed at 3 time points:
Hospital Admission Hospital Discharge 90-day follow-up
measure: Shear Wave Velocity
time frame: Day 0,3,5,7 of Hospitalization
description: Ultrasound shear wave velocity measurements in bowel wall
measure: Need for Re-hospitalization or Surgery within 90 days of discharge
time frame: 90 days post discharge
description: Telephone follow up with subjects 90 days following index hospitalization to assess need for re-hospitalization or surgery
arm group label: Crohn's Inpatients
description: Crohn's Inpatients, with clinical small bowel obstruction All undergo ultrasound stiffness imaging (USI) of distal affected ileum.
arm group label: Crohn's Outpatients
description: Crohn's Outpatients, starting anti-TNF therapy All undergo ultrasound stiffness imaging (USI) at week 0, 6, 14
intervention type: Procedure
intervention name: Ultrasound stiffness imaging
description: Subjects will undergo transabdominal ultrasound of the distal intestine. Distal intestine motion capture will be used for off-line stiffness assessment by two-dimensional speckle tracking. In addition, shear wave imaging will be used for real-time stiffness assessment.
arm group label: Crohn's Inpatients
arm group label: Crohn's Outpatients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ryan W Stidham, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Ryan W. Stidham
investigator title: Principle Investigator
mesh term: Crohn Disease
mesh term: Fibrosis