<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/NCT03264950</url>
  </required_header>
  <id_info>
    <org_study_id>B2017:077</org_study_id>
    <nct_id>NCT03264950</nct_id>
  </id_info>
  <brief_title>Utility of Point Shear-wave Elastography to Assess for Hepatic &amp; Pancreatic Fibrosis in Pediatric CF Patients</brief_title>
  <acronym>CFALD</acronym>
  <official_title>The Utility of Point Shear-wave Elastography to Assess for Hepatic &amp; Pancreatic Fibrosis in Pediatric Cystic Fibrosis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Manitoba</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Diagnosis of hepatic fibrosis is challenging as specific tests for detection of fibrosis in&#xD;
      pediatric Cystic Fibrosis associated liver disease (CFALD) have not been developed and&#xD;
      existing investigations do not correlate well with presence or severity of disease. Using a&#xD;
      Liver biopsy it is difficult to diagnose this condition because of the patchy nature of the&#xD;
      disease. Investigators intend to identify hepatic and pancreatic fibrosis in Cystic Fibrosis&#xD;
      patients using Elastography and correlate this with their biochemical markers as well as&#xD;
      histological findings of patients who have undergone liver biopsy for diagnosis of CFALD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Liver disease is increasingly common in cystic fibrosis (CF). As new therapeutic options&#xD;
      emerge, life expectancy increases and common hepatobiliary manifestations impact on quality&#xD;
      of life and survival of CF patients. Hepatobiliary abnormalities in CF vary in nature and&#xD;
      range from defects attributable to the underlying CFTR gene defect to those related to&#xD;
      systemic disease and malnutrition. Today complications of liver disease represent the third&#xD;
      most frequent cause of disease-related death in patients with CF.&#xD;
&#xD;
      Cystic fibrosis-associated liver disease (CFALD) belongs to the group of common symptoms of&#xD;
      this disease; however, due to the lack of specific and sensitive CFALD diagnostic markers,&#xD;
      the epidemiological data may be incomplete. According to various sources, the prevalence rate&#xD;
      of CFALD, diagnosed on the basis of clinical, biochemical and imaging (ultrasonography)&#xD;
      tests, is 2-37% in children and young adults.&#xD;
&#xD;
      Cirrhosis is a final, irreversible stage of liver damage that leads to the failure of the&#xD;
      organ. While liver biopsy is considered the gold standard to assess for Hepatic Fibrosis; it&#xD;
      is invasive and potentially life threatening. The prognosis and management of chronic liver&#xD;
      disease depends on the extent and progression of liver fibrosis, which constitutes the most&#xD;
      important predictor of disease outcome.&#xD;
&#xD;
      The gold standard for diagnosis and staging of liver fibrosis has been liver biopsy. In&#xD;
      addition to being an invasive procedure with potential complications of bleeding and severe&#xD;
      pain, sampling error is an intrinsic problem due to the small sample size in a heterogeneous&#xD;
      process.7,8 Inter-observer variability also limits diagnostic consistency.9-11 The&#xD;
      development of several blood markers such as platelets, hyaluronic acid, type IV collagen,&#xD;
      aminotransferase/platelet ratio index (APRI) and algorithm based serum models (Fibro Index,&#xD;
      FIB-4, and Fibro Test) have been used but are affected by factors unrelated to the liver.&#xD;
&#xD;
      In the last decade, methods to noninvasively quantify liver fibrosis have been developed. The&#xD;
      first available method was transient elastography (TE).It is a single-element ultrasound&#xD;
      transducer operating at 5 MHz built on the axis of a piston like vibrator. By pushing a&#xD;
      button, low-frequency (50 Hz) transient vibrations are transmitted, and the generated elastic&#xD;
      shear waves propagate through underlying tissues. Pulse-echo ultrasound acquisitions are used&#xD;
      to follow the propagation of the shear wave and to measure its velocity .&#xD;
&#xD;
      Several studies have demonstrated a high accuracy of TE in identifying significant fibrosis&#xD;
      (F&gt; 2) and cirrhosis (F= 4) in patients. It is a novel diagnostic tool that offers a rapid,&#xD;
      non-invasive method for monitoring HF. The device measures liver stiffness by transmitting a&#xD;
      vibration to determine the velocity of an elastic shear wave propagated through liver tissue.&#xD;
&#xD;
      Studies have documented utility of transient elastography in cystic fibrosis patients to&#xD;
      assess hepatic fibrosis and secondary complications.&#xD;
&#xD;
      Newer modalities like Shear wave elastography techniques have been implemented in&#xD;
      conventional real-time ultrasound systems, and several studies have shown their accuracy in&#xD;
      the assessment of liver fibrosis. Shear wave elastography relies on the generation of shear&#xD;
      waves determined by the displacement of tissues induced by the force of a focused ultrasound&#xD;
      beam or by external pressure. The shear waves are lateral waves, with a motion perpendicular&#xD;
      to the direction of the force that has generated them. They travel slowly (between 1 and 10&#xD;
      m/s) and are rapidly attenuated by tissue. The propagation velocity of the shear waves&#xD;
      correlates with the elasticity of tissue .&#xD;
&#xD;
      Compared with TE, these techniques have the advantage of B-mode image guidance; thus, they&#xD;
      can allow the user to choose the best acoustic window for correctly performing an examination&#xD;
      in real time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 1, 2017</start_date>
  <completion_date type="Anticipated">January 31, 2018</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2017</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>
    <intervention_model_description>Patients (&lt;18 years) will be recruited from from the Children's Hospital Winnipeg CF clinic. Charts will be reviewed for demographic and clinical data including blood work. Each patient will undergo shear wave elastography by a trained operator.</intervention_model_description>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Evaluate the diagnostic properties of Shear wave Elastography</measure>
    <time_frame>6 months</time_frame>
    <description>To evaluate the diagnostic properties of Shear wave Elastography (ElastPQ) in children with CF for detection of liver fibrosis.&#xD;
Investigators will look at the values of shearwave elastography and see how it correlates with the fibrosis values obtained on liver biopsy as well as with AST/platelet ratio index</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare findings/fibrosis of Transient Elastography vs ElastPQ</measure>
    <time_frame>6 months</time_frame>
    <description>Investigators will compare degree of fibrosis on Transient Elastography vs Elast PQ to determine correlation .Some patients who have undergone liver biopsy will be correlated to liver fibrosis seen on biopsy.&#xD;
This will allow investigators to determine if Shear wave elastography can reliably detect fibrosis in patients with CFALD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To compare the pancreatic insufficiency/ fecal elastase and transient elastography from pancreas.</measure>
    <time_frame>6 months</time_frame>
    <description>Investigators will see how well pancreatic fibrosis correlates with Fecal Elastase values and pancreatic endocrine function .&#xD;
This will let investigators know if Pancreatic elastography can help them in deciding which patients can have pancreatic insufficiency .</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Cystic Fibrosis</condition>
  <condition>Cystic Fibrosis Liver Disease</condition>
  <condition>Pancreatic Insufficiency Due to Cystic Fibrosis of Pancreas</condition>
  <arm_group>
    <arm_group_label>SIngle Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All patients undergo Elastography. This is a single arm study</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Elastography</intervention_name>
    <description>an ultrasound exam after selecting the best acoustic window, a region of interest (ROI) is placed in an area of the liver perpendicular to the liver capsule, taking care not to include large vasculature or biliary structures.&#xD;
Similarly an acoustic window will be selected for the pancreas as well</description>
    <arm_group_label>SIngle Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &lt;18 years&#xD;
&#xD;
          -  Confirmed diagnosis of cystic fibrosis attending Pediatric cystic fibrosis (CF) Clinic&#xD;
             at Children's Hospital, Winnipeg.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children with age &gt;18 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Quais Mujawar</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Quais Mujawar</last_name>
    <phone>204-787-4950</phone>
    <email>qmujawar@exchange.hsc.mb.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Vini Deora</last_name>
    <phone>204-787-4956</phone>
    <email>vdeora@exchange.hsc.mb.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Winnipeg Children's Hospital</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3A 1S1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <contact>
      <last_name>Quais Mujawar</last_name>
      <phone>204-787-4950</phone>
      <email>qmujawar@exchange.hsc.mb.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>June 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>August 29, 2017</last_update_submitted>
  <last_update_submitted_qc>August 29, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manitoba</investigator_affiliation>
    <investigator_full_name>Quais Mujawar</investigator_full_name>
    <investigator_title>Pediatric Gastroenterologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Exocrine Pancreatic Insufficiency</mesh_term>
    <mesh_term>Fibrosis</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/NCT03264950
org study id: B2017:077
nct id: NCT03264950
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Diagnosis of hepatic fibrosis is challenging as specific tests for detection of fibrosis in
      pediatric Cystic Fibrosis associated liver disease (CFALD) have not been developed and
      existing investigations do not correlate well with presence or severity of disease. Using a
      Liver biopsy it is difficult to diagnose this condition because of the patchy nature of the
      disease. Investigators intend to identify hepatic and pancreatic fibrosis in Cystic Fibrosis
      patients using Elastography and correlate this with their biochemical markers as well as
      histological findings of patients who have undergone liver biopsy for diagnosis of CFALD.
Liver disease is increasingly common in cystic fibrosis (CF). As new therapeutic options
      emerge, life expectancy increases and common hepatobiliary manifestations impact on quality
      of life and survival of CF patients. Hepatobiliary abnormalities in CF vary in nature and
      range from defects attributable to the underlying CFTR gene defect to those related to
      systemic disease and malnutrition. Today complications of liver disease represent the third
      most frequent cause of disease-related death in patients with CF.

      Cystic fibrosis-associated liver disease (CFALD) belongs to the group of common symptoms of
      this disease; however, due to the lack of specific and sensitive CFALD diagnostic markers,
      the epidemiological data may be incomplete. According to various sources, the prevalence rate
      of CFALD, diagnosed on the basis of clinical, biochemical and imaging (ultrasonography)
      tests, is 2-37% in children and young adults.

      Cirrhosis is a final, irreversible stage of liver damage that leads to the failure of the
      organ. While liver biopsy is considered the gold standard to assess for Hepatic Fibrosis; it
      is invasive and potentially life threatening. The prognosis and management of chronic liver
      disease depends on the extent and progression of liver fibrosis, which constitutes the most
      important predictor of disease outcome.

      The gold standard for diagnosis and staging of liver fibrosis has been liver biopsy. In
      addition to being an invasive procedure with potential complications of bleeding and severe
      pain, sampling error is an intrinsic problem due to the small sample size in a heterogeneous
      process.7,8 Inter-observer variability also limits diagnostic consistency.9-11 The
      development of several blood markers such as platelets, hyaluronic acid, type IV collagen,
      aminotransferase/platelet ratio index (APRI) and algorithm based serum models (Fibro Index,
      FIB-4, and Fibro Test) have been used but are affected by factors unrelated to the liver.

      In the last decade, methods to noninvasively quantify liver fibrosis have been developed. The
      first available method was transient elastography (TE).It is a single-element ultrasound
      transducer operating at 5 MHz built on the axis of a piston like vibrator. By pushing a
      button, low-frequency (50 Hz) transient vibrations are transmitted, and the generated elastic
      shear waves propagate through underlying tissues. Pulse-echo ultrasound acquisitions are used
      to follow the propagation of the shear wave and to measure its velocity .

      Several studies have demonstrated a high accuracy of TE in identifying significant fibrosis
      (F> 2) and cirrhosis (F= 4) in patients. It is a novel diagnostic tool that offers a rapid,
      non-invasive method for monitoring HF. The device measures liver stiffness by transmitting a
      vibration to determine the velocity of an elastic shear wave propagated through liver tissue.

      Studies have documented utility of transient elastography in cystic fibrosis patients to
      assess hepatic fibrosis and secondary complications.

      Newer modalities like Shear wave elastography techniques have been implemented in
      conventional real-time ultrasound systems, and several studies have shown their accuracy in
      the assessment of liver fibrosis. Shear wave elastography relies on the generation of shear
      waves determined by the displacement of tissues induced by the force of a focused ultrasound
      beam or by external pressure. The shear waves are lateral waves, with a motion perpendicular
      to the direction of the force that has generated them. They travel slowly (between 1 and 10
      m/s) and are rapidly attenuated by tissue. The propagation velocity of the shear waves
      correlates with the elasticity of tissue .

      Compared with TE, these techniques have the advantage of B-mode image guidance; thus, they
      can allow the user to choose the best acoustic window for correctly performing an examination
      in real time.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Patients (<18 years) will be recruited from from the Children's Hospital Winnipeg CF clinic. Charts will be reviewed for demographic and clinical data including blood work. Each patient will undergo shear wave elastography by a trained operator.
primary purpose: Diagnostic
masking: None (Open Label)
measure: Evaluate the diagnostic properties of Shear wave Elastography
time frame: 6 months
description: To evaluate the diagnostic properties of Shear wave Elastography (ElastPQ) in children with CF for detection of liver fibrosis.
Investigators will look at the values of shearwave elastography and see how it correlates with the fibrosis values obtained on liver biopsy as well as with AST/platelet ratio index
measure: To compare findings/fibrosis of Transient Elastography vs ElastPQ
time frame: 6 months
description: Investigators will compare degree of fibrosis on Transient Elastography vs Elast PQ to determine correlation .Some patients who have undergone liver biopsy will be correlated to liver fibrosis seen on biopsy.
This will allow investigators to determine if Shear wave elastography can reliably detect fibrosis in patients with CFALD
measure: To compare the pancreatic insufficiency/ fecal elastase and transient elastography from pancreas.
time frame: 6 months
description: Investigators will see how well pancreatic fibrosis correlates with Fecal Elastase values and pancreatic endocrine function .
This will let investigators know if Pancreatic elastography can help them in deciding which patients can have pancreatic insufficiency .
arm group label: SIngle Arm
arm group type: Other
description: All patients undergo Elastography. This is a single arm study
intervention type: Diagnostic Test
intervention name: Elastography
description: an ultrasound exam after selecting the best acoustic window, a region of interest (ROI) is placed in an area of the liver perpendicular to the liver capsule, taking care not to include large vasculature or biliary structures.
Similarly an acoustic window will be selected for the pancreas as well
arm group label: SIngle Arm
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Quais Mujawar
role: Principal Investigator
affiliation: University of Manitoba
last name: Quais Mujawar
phone: 204-787-4950
email: qmujawar@exchange.hsc.mb.ca
last name: Vini Deora
phone: 204-787-4956
email: vdeora@exchange.hsc.mb.ca
facility: 
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Manitoba
investigator full name: Quais Mujawar
investigator title: Pediatric Gastroenterologist
mesh term: Cystic Fibrosis
mesh term: Liver Diseases
mesh term: Exocrine Pancreatic Insufficiency
mesh term: Fibrosis
sharing ipd: No