<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/NCT02201537</url>
  </required_header>
  <id_info>
    <org_study_id>2012-A01070-43</org_study_id>
    <nct_id>NCT02201537</nct_id>
  </id_info>
  <brief_title>Kidney Disease and Ultrasound Imaging</brief_title>
  <acronym>Imag-NCT</acronym>
  <official_title>Non-invasive Diagnosis of Chronic Kidney Disease in Renal Transplants Kidney Transplanted Using Ultrasound Functional Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondation de l'Avenir</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bracco Imaging S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The hypothesis of our study is that a correlation exists between the couple ultrasound&#xD;
      elastography- renal perfusion estimated with contrast-enhanced ultrasound and the degree of&#xD;
      fibrosis estimated in a semi-quantitative way in 4 stages (0; 25 %; 25-50 %; &gt; 50 %), as&#xD;
      elastography alone did not allow to differentiate moderated fibrosis at 3 months in our&#xD;
      feasibility study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Kidney transplant patients are exposed to long-term immunosuppressive therapy, and have an&#xD;
      increased risk of infections and cancer, while a lack of treatment increases the risk of&#xD;
      rejection. The development of imaging techniques to characterize the status of the graft&#xD;
      remains a challenge in transplantation. Ideally, they should identify complications (acute&#xD;
      rejection, chronic allograft nephropathy, nephrotoxicity ...) without the need for invasive&#xD;
      procedures and thus lead to better customization of immunosuppressive therapy.&#xD;
&#xD;
      The post-transplant follow-up is based on the monitoring of graft function. Impaired function&#xD;
      suggests the possibility of a complication, but requires confirmation by an invasive&#xD;
      procedure such as renal biopsy. In addition, the diagnosis remains complex at a relatively&#xD;
      advanced stage of the process due to damage to the graft parenchyma. To anticipate the&#xD;
      altered function and detect subclinical lesions, screening biopsies have been used to&#xD;
      diagnose chronic rejection. By definition, screening for subclinical lesions can not be based&#xD;
      on any biological parameter; the diagnosis of subclinical complications thus requires&#xD;
      performing multiple systematic biopsies, which are scheduled at 3 months and 1 year.&#xD;
&#xD;
      Doppler ultrasound is an imaging method of choice for the study of renal transplant, but it&#xD;
      cannot diagnose the NCT due to the absence of specific findings. The lack of early diagnostic&#xD;
      test for NCT is a major obstacle to the development and evaluation of new therapeutic options&#xD;
      to prevent, slow or stabilize renal fibrosis. It is therefore necessary to develop a&#xD;
      non-invasive imaging technique for the early diagnosis of NCT.&#xD;
&#xD;
      Ultrasound elastography is a technique that allows tissue stiffness measurements and provides&#xD;
      a parametric picture.&#xD;
&#xD;
      The main objective of our study is to evaluate the performances of elastography and&#xD;
      measurement of renal perfusion (area under the ROC curve) to diagnose the NCT and determine&#xD;
      for each both measures a threshold to maximize the sensitivity. These performances will be&#xD;
      evaluated at 3 months and 12 months. The results can also be compared to other imaging&#xD;
      modalities such as functional MRI, and to clinical events (obstruction, infection…).&#xD;
&#xD;
      Functional ultrasound imaging should identify diagnostic and prognostic criteria of NCT, and&#xD;
      enable the development of less invasive therapeutic protocols to evaluate new therapeutic&#xD;
      approaches&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 19, 2013</start_date>
  <completion_date type="Actual">March 19, 2016</completion_date>
  <primary_completion_date type="Actual">March 19, 2016</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>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>renal Elastography</measure>
    <time_frame>3 months</time_frame>
    <description>The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient.&#xD;
The ultrasound functional imaging will be performed at 15 days, 3 and 12 months after transplantation.&#xD;
The functional imaging examinations will be held as follows:&#xD;
Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal Elastography and contrast-enhanced US</measure>
    <time_frame>12 months</time_frame>
    <description>The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient.&#xD;
The ultrasound functional imaging will be performed at 15 days, 3 and 12 months after transplantation.&#xD;
The functional imaging examinations will be held as follows:&#xD;
Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>renal Elastography</measure>
    <time_frame>3 months</time_frame>
    <description>Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between renal elastography and perfusion and degree of fibrosis and renal function</measure>
    <time_frame>12 months</time_frame>
    <description>Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>renal Elastography in patients with chronic kidney disease</measure>
    <time_frame>12 months</time_frame>
    <description>this two measures will be express in evolution percentage at J15 and 3 months. The evolution percentage will be compared with imaging of patient with chronic kidney disease to determine if elastography and renal perfusion can predict chronic kidney disease at one year.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">141</enrollment>
  <condition>Recipient of Kidney Transplant</condition>
  <arm_group>
    <arm_group_label>Imag-NCT</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The ultrasound functional imaging will be performed at J15 (before the patient is discharged from service Transplantation) and at 3 and 12 months after the transplant.&#xD;
The functional imaging examinations will be held as follows:&#xD;
1st stage - the conventional Doppler ultrasound:&#xD;
2nd stage - the elastography:.&#xD;
Step 3 - CEUS: It is performed on an ultrasound machine with a specific module with the same probes as conventional ultrasound. It requires the injection of 1.5 ml of SonoVue ®, a contrast ultrasound.&#xD;
Renal biopsy will be performed after the functional ultrasound at 3 and 12 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>renal echography</intervention_name>
    <description>Renal biopsy will be performed at 3 and 12 months.&#xD;
The functional imaging examinations will be held as follows:&#xD;
Step 1: the conventional Doppler ultrasound Step 2: ultrasound elastography Step 3: CEUS</description>
    <arm_group_label>Imag-NCT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years;&#xD;
&#xD;
          -  Patient with informed consent;&#xD;
&#xD;
          -  Recipient of a living donor graft or cadaveric donor patient;&#xD;
&#xD;
          -  No contraindication for biopsy of the graft;&#xD;
&#xD;
          -  No contraindication to the injection of SonoVue ®:&#xD;
&#xD;
               -  hypersensitivity to sulfur hexafluoride&#xD;
&#xD;
               -  acute coronary syndrome, unstable ischemic heart disease (myocardial infarction&#xD;
                  phase formation or evolution, typical resting angina in the previous 7 days,&#xD;
                  significant worsening of cardiac symptoms in the previous 7 days, recent&#xD;
                  intervention on the coronary arteries or another factor suggesting clinical&#xD;
                  instability (eg, recent deterioration of ECG changes in clinical or laboratory&#xD;
                  parameters), acute heart failure, stage III or IV heart failure, severe&#xD;
                  arrhythmias.&#xD;
&#xD;
               -  right-left shunt, severe pulmonary hypertension (PAP&gt; 90 mmHg), uncontrolled&#xD;
                  systemic hypertension, respiratory distress syndrome&#xD;
&#xD;
          -  Affiliated to a social security scheme&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to participate in the study;&#xD;
&#xD;
          -  Inability / refusal to give informed consent;&#xD;
&#xD;
          -  contraindication for biopsy testing graft;&#xD;
&#xD;
          -  Presence of a contraindication to the injection of SonoVue ®.&#xD;
&#xD;
          -  Presence of a peripheral venous access in a non-restricted already infused patient,&#xD;
             not pickable under ultrasound&#xD;
&#xD;
          -  Breastfeeding, pregnancy&#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_official>
    <last_name>Jean-Michel CORREAS, PUPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Necker Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NECKER Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>December 20, 2017</last_update_submitted>
  <last_update_submitted_qc>December 20, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ultrasound functional imaging</keyword>
  <keyword>Chronic kidney Nephropathy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</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/NCT02201537
org study id: 2012-A01070-43
nct id: NCT02201537
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The hypothesis of our study is that a correlation exists between the couple ultrasound
      elastography- renal perfusion estimated with contrast-enhanced ultrasound and the degree of
      fibrosis estimated in a semi-quantitative way in 4 stages (0; 25 %; 25-50 %; > 50 %), as
      elastography alone did not allow to differentiate moderated fibrosis at 3 months in our
      feasibility study.
Kidney transplant patients are exposed to long-term immunosuppressive therapy, and have an
      increased risk of infections and cancer, while a lack of treatment increases the risk of
      rejection. The development of imaging techniques to characterize the status of the graft
      remains a challenge in transplantation. Ideally, they should identify complications (acute
      rejection, chronic allograft nephropathy, nephrotoxicity ...) without the need for invasive
      procedures and thus lead to better customization of immunosuppressive therapy.

      The post-transplant follow-up is based on the monitoring of graft function. Impaired function
      suggests the possibility of a complication, but requires confirmation by an invasive
      procedure such as renal biopsy. In addition, the diagnosis remains complex at a relatively
      advanced stage of the process due to damage to the graft parenchyma. To anticipate the
      altered function and detect subclinical lesions, screening biopsies have been used to
      diagnose chronic rejection. By definition, screening for subclinical lesions can not be based
      on any biological parameter; the diagnosis of subclinical complications thus requires
      performing multiple systematic biopsies, which are scheduled at 3 months and 1 year.

      Doppler ultrasound is an imaging method of choice for the study of renal transplant, but it
      cannot diagnose the NCT due to the absence of specific findings. The lack of early diagnostic
      test for NCT is a major obstacle to the development and evaluation of new therapeutic options
      to prevent, slow or stabilize renal fibrosis. It is therefore necessary to develop a
      non-invasive imaging technique for the early diagnosis of NCT.

      Ultrasound elastography is a technique that allows tissue stiffness measurements and provides
      a parametric picture.

      The main objective of our study is to evaluate the performances of elastography and
      measurement of renal perfusion (area under the ROC curve) to diagnose the NCT and determine
      for each both measures a threshold to maximize the sensitivity. These performances will be
      evaluated at 3 months and 12 months. The results can also be compared to other imaging
      modalities such as functional MRI, and to clinical events (obstruction, infection…).

      Functional ultrasound imaging should identify diagnostic and prognostic criteria of NCT, and
      enable the development of less invasive therapeutic protocols to evaluate new therapeutic
      approaches
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: renal Elastography
time frame: 3 months
description: The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient.
The ultrasound functional imaging will be performed at 15 days, 3 and 12 months after transplantation.
The functional imaging examinations will be held as follows:
Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS
measure: Renal Elastography and contrast-enhanced US
time frame: 12 months
description: The assessment of renal function is performed by the serum creatinine and calculation of glomerular filtration rate estimated by the formula Modified Diet in Renal Disease (MDRD) 4-parameter at 3 and 12 months post-transplantation. In addition, a measure of glomerular filtration rate using the technique to iohexol is performed routinely at 12 months post-transplant as part of routine monitoring of transplant patient.
The ultrasound functional imaging will be performed at 15 days, 3 and 12 months after transplantation.
The functional imaging examinations will be held as follows:
Step 1: the conventional Doppler ultrasound 2nd step: the ultrasound elastography Step 3 : CEUS
measure: renal Elastography
time frame: 3 months
description: Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation
measure: Correlation between renal elastography and perfusion and degree of fibrosis and renal function
time frame: 12 months
description: Correlation between elastography and renal function with degree of fibrosis and renal function will be calculate using Pearson coefficient of correlation
measure: renal Elastography in patients with chronic kidney disease
time frame: 12 months
description: this two measures will be express in evolution percentage at J15 and 3 months. The evolution percentage will be compared with imaging of patient with chronic kidney disease to determine if elastography and renal perfusion can predict chronic kidney disease at one year.
arm group label: Imag-NCT
arm group type: Other
description: The ultrasound functional imaging will be performed at J15 (before the patient is discharged from service Transplantation) and at 3 and 12 months after the transplant.
The functional imaging examinations will be held as follows:
1st stage - the conventional Doppler ultrasound:
2nd stage - the elastography:.
Step 3 - CEUS: It is performed on an ultrasound machine with a specific module with the same probes as conventional ultrasound. It requires the injection of 1.5 ml of SonoVue ®, a contrast ultrasound.
Renal biopsy will be performed after the functional ultrasound at 3 and 12 months.
intervention type: Device
intervention name: renal echography
description: Renal biopsy will be performed at 3 and 12 months.
The functional imaging examinations will be held as follows:
Step 1: the conventional Doppler ultrasound Step 2: ultrasound elastography Step 3: CEUS
arm group label: Imag-NCT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Michel CORREAS, PUPH
role: Principal Investigator
affiliation: Necker Hospital
facility: 
country: France
responsible party type: Sponsor
mesh term: Kidney Diseases