<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/NCT03822442</url>
  </required_header>
  <id_info>
    <org_study_id>11408</org_study_id>
    <nct_id>NCT03822442</nct_id>
  </id_info>
  <brief_title>MRI to Predict Rejection and Failure in Transplant and Cardiomyopathy Patients</brief_title>
  <official_title>MRI to Predict Rejection and Failure in Transplant and Cardiomyopathy Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laura Olivieri</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's National Research Institute</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>
      Overall Research Strategy of this protocol is to refine and validate noninvasive CMR imaging&#xD;
      sequences with invasive hemodynamic and pathology results to create a comprehensive,&#xD;
      noninvasive, radiation-reduced regimen for pediatric cardiomyopathy and cardiac transplant&#xD;
      assessment. We were the first to perform MR-guided cardiac catheterization in US children,&#xD;
      and have accumulated the largest US experience, having performed over 75 procedures to date.&#xD;
      Our unique experience puts us in strong position to leverage this technology to improve care&#xD;
      of children with cardiomyopathy and transplant. Using an integrated approach, we will&#xD;
      simultaneously (1) validate imaging measures of cardiac edema and fibrosis by correlating T1&#xD;
      and T2 map images with endomyocardial biopsy (EMB) results in Aim 1; (2) overlay T1, T2 map&#xD;
      images into our x-ray system to display &quot;hotspots&quot; of T1 and T2 abnormalities to guide EMB in&#xD;
      Aim 2; and (3) obtain radiation-free hemodynamic data in a highly vulnerable pediatric&#xD;
      population by using CMR to guide catheter manipulation in the ICMR suite in Aim 3.&#xD;
&#xD;
      Age and diagnosis-matched historical controls will be identified from the last 10 years at&#xD;
      Children's National as a control population for specific purposes of comparing (1) EMB yield&#xD;
      without image overlay and (2) Radiation exposure during X-ray guided right heart&#xD;
      catheterization. Identical information will be obtained and stored in the same 45CFR&#xD;
      compliant database. Historical controls will be identified from the cardiac catheterization&#xD;
      database by searching for age and diagnosis. A waiver of consent will be applicable here, as&#xD;
      it would be inconvenient, insensitive and not feasible to consent families who have already&#xD;
      undergone treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anesthesia and Vascular Access After final review of protocol eligibility and of MRI safety,&#xD;
      vascular access is obtained and sheaths are secured and covered with a sterile drape for&#xD;
      transfer to the MRI. The catheterization is performed with continuous recording of&#xD;
      electrocardiogram signals, transcutaneous hemoglobin (&quot;pulse&quot;) oximetry, and under direct&#xD;
      observation of an anesthesia licensed independent provider.&#xD;
&#xD;
      Diagnostic Cardiac MRI Before MRI catheterization begins, a focused cardiac MRI is performed&#xD;
      to understand cardiac function and localize the proposed catheter trajectory from the access&#xD;
      site into the targeted cardiovascular chambers.&#xD;
&#xD;
      MRI-guided catheterization Next during real-time MRI, a passive catheter is advanced from the&#xD;
      access site into the targeted cardiovascular chambers under imaging guidance. Hemodynamic&#xD;
      measurements (using fluid-filled transducers connected to the catheters) and blood hemoglobin&#xD;
      saturation specimens are obtained from targeted cardiovascular chambers. Additional&#xD;
      clinically-indicated and, if time allows, up to 30 minutes of research MRI is then performed&#xD;
      before the subject is returned to the X-ray system.&#xD;
&#xD;
      Research MR Imaging Additional research cardiac MRI imaging to determine T1 and T2 values is&#xD;
      undertaken next, with 6 short axis slices and one long axis slice positions identified for T1&#xD;
      map and T2 map acquisitions. The ICMR laboratory has a robust experience with acquisition of&#xD;
      parametric mapping sequences. T1 and T2 maps will provide a roadmap for the cardiac biopsy&#xD;
      that the patient requires in the xray suite.&#xD;
&#xD;
      Image Fusion to Guide Endomyocardial Biopsy At the conclusion of the MR imaging and MR-guided&#xD;
      right heart catheterization procedure, the subject is returned to the X-ray suite for cardiac&#xD;
      biopsy. Some cardiac biopsies are obtained in the usual fashion, and some biopsy specimens&#xD;
      are obtained using image overlay software to display the regions of abnormal T1 and T2 onto&#xD;
      the fluoroscopy system.&#xD;
&#xD;
      Conclusion of the procedure Following standard of care EMB, standard of care coronary&#xD;
      angiography is obtained when if clinically indicated, all catheters and sheaths are removed&#xD;
      and the subject is observed for complications in the cardiac procedure recovery unit or&#xD;
      intensive care unit for at least 6 hours.&#xD;
&#xD;
      Diagnostic Echocardiogram Standard clinical data with strain analysis will be collected from&#xD;
      the echocardiogram that is performed as a standard of care. Patients undergo a clinically&#xD;
      indicated echocardiogram exam following the catheterization procedure in the Cardiac Post&#xD;
      Recovery Unit (CPRU).&#xD;
&#xD;
      Blood Tests Serum for creatinine blood test will be collected at the time the clinically&#xD;
      indicated IV is placed. Creatinine Is the standard test used at Children's National to assess&#xD;
      kidney function. A total of 1cc of blood will be drawn to complete the test.&#xD;
&#xD;
      For subjects who consent to the optional study, an additional 5cc of blood work will be drawn&#xD;
      at the time that the intravascular catheter is inserted for the clinically indicated cardiac&#xD;
      catheterization procedure. The blood samples will be identified with the study ID number&#xD;
      only, and will be stored in a secure freezer owned and maintained by the department of&#xD;
      cardiology located at the Sheikh Zayed campus. This blood will be used to identify serum&#xD;
      biomarkers, and to validate the potential use for diagnostic purposes.&#xD;
&#xD;
      Follow-up procedures At the conclusion of the procedure, the subject is returned to the X-ray&#xD;
      table and all catheters are removed. The subject is observed for complications in an advanced&#xD;
      nursing recovery unit or intensive care unit for at least 6 hours. The subject will be&#xD;
      assessed for early and late complications at the time of discharge, and again approximately&#xD;
      2-6 weeks ± 7 days post procedure.&#xD;
&#xD;
      MRI Image Analysis In all cardiomyopathy and heart transplant patients, T1 measurements will&#xD;
      be performed using offline analysis software according to our laboratory's measurement SOP&#xD;
      for parametric maps. In heart transplant patients only, T2 measurements will be performed&#xD;
      according to our laboratory's measurement SOP for parametric maps. Following measurements,&#xD;
      images will be created for Image Overlay onto the fluoroscopy for patients undergoing&#xD;
      clinically-indicated cardiac biopsy following the catheterization.&#xD;
&#xD;
      Biopsy Sample Analysis All biopsy samples will be evaluated clinically for evidence of&#xD;
      cellular rejection, and a clinical report will be generated per clinical standard of care. In&#xD;
      addition, each of the samples will undergo a separate staining procedure to identify regions&#xD;
      of fibrosis. Digital images will be taken of the stained samples. Image processing software&#xD;
      will be used to quantify percent fibrosis.&#xD;
&#xD;
      Historical Controls (for radiation exposure comparison, and biopsy yield comparison) Age and&#xD;
      diagnosis-matched historical controls will be identified from the last 10 years at Children's&#xD;
      National as a control population for specific purposes of comparing (1) EMB yield without&#xD;
      image overlay and (2) Radiation exposure during X-ray guided right heart catheterization.&#xD;
      Identical information will be obtained and stored in the same 45CFR compliant database.&#xD;
      Historical controls will be identified from the cardiac catheterization database by searching&#xD;
      for age and diagnosis. A waiver of consent will be applicable here, as it would be&#xD;
      inconvenient, insensitive and not feasible to consent families who have already undergone&#xD;
      treatment.&#xD;
&#xD;
      Subjects will not be provided additional information as a result of this research study.&#xD;
&#xD;
      Data will be reviewed in aggregate generating generalizable knowledge not applicable to an&#xD;
      individual subject&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>Correlate MRI imaging results to biopsy results Correlate MRI imaging with endomyocardial biopsy</measure>
    <time_frame>At the end of each catheterization procedure through study completion,up to 5 years</time_frame>
    <description>Correlate MRI imaging sequences that can detect inflammation and fibrosis to quantities of inflammation and fibrosis seen on biopsy specimens taken from the same region.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare yield of biopsy specimen collection using x-ray vs x-ray fused MRI images</measure>
    <time_frame>At the end of each catheterization procedure through study completion,up to 5 years</time_frame>
    <description>To compare the accuracy and yield of biopsy specimens collected for detection of rejection by using standard of care, unguided x-ray imaging for the biopsy to the accuracy and yield results of specimens collected using x-ray fused with MR imaging overlay for guidance towards &quot;hotspots&quot; of fibrosis and inflammation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiation exposure</measure>
    <time_frame>At the end of each catheterization procedure through study completion,up to 5 years</time_frame>
    <description>To compare radiation exposure in this cohort of subjects (pre and post heart transplant) with recent historical controls undergoing matched invasive cardiology procedures at Children's National Medical Center prior to use of MR-guided cardiac catheterization.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Heart Failure</condition>
  <condition>Cardiac Imaging Techniques</condition>
  <condition>Congenital Heart Defects</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      5cc of blood will be collected if subject consent to the optional study. This blood will be&#xD;
      used to identify serum biomarkers, and to validate the potential use for diagnostic purposes.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals referred to Children's National Medical Center with heart transplant or&#xD;
        cardiomyopathy (i.e. &quot;pre-transplant&quot;) to undergo clinically-indicated cardiac&#xD;
        catheterization will be considered candidates for inclusion.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children and adults of any age with heart transplant, suspected or confirmed&#xD;
             cardiomyopathy&#xD;
&#xD;
          -  Undergoing clinically-indicated (&quot;medically necessary&quot;) cardiovascular catheterization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiovascular instability including hemodynamic instability (such as requiring&#xD;
             significant vasoactive infusion support) or mechanical hemodynamic support.&#xD;
&#xD;
          -  Women who are pregnant&#xD;
&#xD;
          -  Women who are nursing and who do not plan to discard breast milk for 24 hours&#xD;
&#xD;
          -  Exclusion criteria for MRI&#xD;
&#xD;
               -  Central nervous system aneurysm clips&#xD;
&#xD;
               -  Implanted neural stimulator&#xD;
&#xD;
               -  Implanted cardiac pacemaker or defibrillator which are not MR safe or MR&#xD;
                  conditional according to the manufacturer&#xD;
&#xD;
               -  Cochlear implant&#xD;
&#xD;
               -  Ocular foreign body (e.g. metal shavings)&#xD;
&#xD;
               -  Implanted Insulin pump&#xD;
&#xD;
               -  Metal shrapnel or bullet.&#xD;
&#xD;
          -  Exclusion criteria for Gadolinium&#xD;
&#xD;
               -  Renal disease with estimated glomerular filtration rate [eGFR] &lt; 30 ml/min/1.73&#xD;
                  m2 body surface area&#xD;
&#xD;
        The eGFR will be used to estimate renal function if reported by the laboratory.&#xD;
&#xD;
        The Schwartz equation 33 for estimation of GFR in children as recommended by the NKDEP is&#xD;
        as follows:&#xD;
&#xD;
        GFR (mL/min/1.73 m2) = (k × height) / serum creatinine concentration&#xD;
&#xD;
        where k = constant defined as follows: k = 0.33 in premature infants k = 0.45 in term&#xD;
        infants to 1 year of age k = 0.55 in children to 13 years of age k = 0.70 in adolescent&#xD;
        males (not females because of the presumed increase in male muscle mass, the constant&#xD;
        remains 0.55 for females) Height in cm Serum creatinine in mg/dL&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laura Olivieri, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's National</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Laura Olivieri, MD</last_name>
    <phone>202-476-2020</phone>
    <email>lolivieri@childrensnational.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joshua Kanter, MD</last_name>
    <phone>202-476-2020</phone>
    <email>jkanter@childrensnational.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children's National Health System</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>July 21, 2022</last_update_submitted>
  <last_update_submitted_qc>July 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Children's National Research Institute</investigator_affiliation>
    <investigator_full_name>Laura Olivieri</investigator_full_name>
    <investigator_title>Associate Professor of Pediatrics/Cardiologist</investigator_title>
  </responsible_party>
  <keyword>Cardiomyopathy, cardiomegaly</keyword>
  <keyword>cardiac transplant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Heart Defects, Congenital</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/NCT03822442
org study id: 11408
nct id: NCT03822442
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Overall Research Strategy of this protocol is to refine and validate noninvasive CMR imaging
      sequences with invasive hemodynamic and pathology results to create a comprehensive,
      noninvasive, radiation-reduced regimen for pediatric cardiomyopathy and cardiac transplant
      assessment. We were the first to perform MR-guided cardiac catheterization in US children,
      and have accumulated the largest US experience, having performed over 75 procedures to date.
      Our unique experience puts us in strong position to leverage this technology to improve care
      of children with cardiomyopathy and transplant. Using an integrated approach, we will
      simultaneously (1) validate imaging measures of cardiac edema and fibrosis by correlating T1
      and T2 map images with endomyocardial biopsy (EMB) results in Aim 1; (2) overlay T1, T2 map
      images into our x-ray system to display "hotspots" of T1 and T2 abnormalities to guide EMB in
      Aim 2; and (3) obtain radiation-free hemodynamic data in a highly vulnerable pediatric
      population by using CMR to guide catheter manipulation in the ICMR suite in Aim 3.

      Age and diagnosis-matched historical controls will be identified from the last 10 years at
      Children's National as a control population for specific purposes of comparing (1) EMB yield
      without image overlay and (2) Radiation exposure during X-ray guided right heart
      catheterization. Identical information will be obtained and stored in the same 45CFR
      compliant database. Historical controls will be identified from the cardiac catheterization
      database by searching for age and diagnosis. A waiver of consent will be applicable here, as
      it would be inconvenient, insensitive and not feasible to consent families who have already
      undergone treatment.
Anesthesia and Vascular Access After final review of protocol eligibility and of MRI safety,
      vascular access is obtained and sheaths are secured and covered with a sterile drape for
      transfer to the MRI. The catheterization is performed with continuous recording of
      electrocardiogram signals, transcutaneous hemoglobin ("pulse") oximetry, and under direct
      observation of an anesthesia licensed independent provider.

      Diagnostic Cardiac MRI Before MRI catheterization begins, a focused cardiac MRI is performed
      to understand cardiac function and localize the proposed catheter trajectory from the access
      site into the targeted cardiovascular chambers.

      MRI-guided catheterization Next during real-time MRI, a passive catheter is advanced from the
      access site into the targeted cardiovascular chambers under imaging guidance. Hemodynamic
      measurements (using fluid-filled transducers connected to the catheters) and blood hemoglobin
      saturation specimens are obtained from targeted cardiovascular chambers. Additional
      clinically-indicated and, if time allows, up to 30 minutes of research MRI is then performed
      before the subject is returned to the X-ray system.

      Research MR Imaging Additional research cardiac MRI imaging to determine T1 and T2 values is
      undertaken next, with 6 short axis slices and one long axis slice positions identified for T1
      map and T2 map acquisitions. The ICMR laboratory has a robust experience with acquisition of
      parametric mapping sequences. T1 and T2 maps will provide a roadmap for the cardiac biopsy
      that the patient requires in the xray suite.

      Image Fusion to Guide Endomyocardial Biopsy At the conclusion of the MR imaging and MR-guided
      right heart catheterization procedure, the subject is returned to the X-ray suite for cardiac
      biopsy. Some cardiac biopsies are obtained in the usual fashion, and some biopsy specimens
      are obtained using image overlay software to display the regions of abnormal T1 and T2 onto
      the fluoroscopy system.

      Conclusion of the procedure Following standard of care EMB, standard of care coronary
      angiography is obtained when if clinically indicated, all catheters and sheaths are removed
      and the subject is observed for complications in the cardiac procedure recovery unit or
      intensive care unit for at least 6 hours.

      Diagnostic Echocardiogram Standard clinical data with strain analysis will be collected from
      the echocardiogram that is performed as a standard of care. Patients undergo a clinically
      indicated echocardiogram exam following the catheterization procedure in the Cardiac Post
      Recovery Unit (CPRU).

      Blood Tests Serum for creatinine blood test will be collected at the time the clinically
      indicated IV is placed. Creatinine Is the standard test used at Children's National to assess
      kidney function. A total of 1cc of blood will be drawn to complete the test.

      For subjects who consent to the optional study, an additional 5cc of blood work will be drawn
      at the time that the intravascular catheter is inserted for the clinically indicated cardiac
      catheterization procedure. The blood samples will be identified with the study ID number
      only, and will be stored in a secure freezer owned and maintained by the department of
      cardiology located at the Sheikh Zayed campus. This blood will be used to identify serum
      biomarkers, and to validate the potential use for diagnostic purposes.

      Follow-up procedures At the conclusion of the procedure, the subject is returned to the X-ray
      table and all catheters are removed. The subject is observed for complications in an advanced
      nursing recovery unit or intensive care unit for at least 6 hours. The subject will be
      assessed for early and late complications at the time of discharge, and again approximately
      2-6 weeks ± 7 days post procedure.

      MRI Image Analysis In all cardiomyopathy and heart transplant patients, T1 measurements will
      be performed using offline analysis software according to our laboratory's measurement SOP
      for parametric maps. In heart transplant patients only, T2 measurements will be performed
      according to our laboratory's measurement SOP for parametric maps. Following measurements,
      images will be created for Image Overlay onto the fluoroscopy for patients undergoing
      clinically-indicated cardiac biopsy following the catheterization.

      Biopsy Sample Analysis All biopsy samples will be evaluated clinically for evidence of
      cellular rejection, and a clinical report will be generated per clinical standard of care. In
      addition, each of the samples will undergo a separate staining procedure to identify regions
      of fibrosis. Digital images will be taken of the stained samples. Image processing software
      will be used to quantify percent fibrosis.

      Historical Controls (for radiation exposure comparison, and biopsy yield comparison) Age and
      diagnosis-matched historical controls will be identified from the last 10 years at Children's
      National as a control population for specific purposes of comparing (1) EMB yield without
      image overlay and (2) Radiation exposure during X-ray guided right heart catheterization.
      Identical information will be obtained and stored in the same 45CFR compliant database.
      Historical controls will be identified from the cardiac catheterization database by searching
      for age and diagnosis. A waiver of consent will be applicable here, as it would be
      inconvenient, insensitive and not feasible to consent families who have already undergone
      treatment.

      Subjects will not be provided additional information as a result of this research study.

      Data will be reviewed in aggregate generating generalizable knowledge not applicable to an
      individual subject
observational model: Cohort
time perspective: Prospective
measure: Correlate MRI imaging results to biopsy results Correlate MRI imaging with endomyocardial biopsy
time frame: At the end of each catheterization procedure through study completion,up to 5 years
description: Correlate MRI imaging sequences that can detect inflammation and fibrosis to quantities of inflammation and fibrosis seen on biopsy specimens taken from the same region.
measure: Compare yield of biopsy specimen collection using x-ray vs x-ray fused MRI images
time frame: At the end of each catheterization procedure through study completion,up to 5 years
description: To compare the accuracy and yield of biopsy specimens collected for detection of rejection by using standard of care, unguided x-ray imaging for the biopsy to the accuracy and yield results of specimens collected using x-ray fused with MR imaging overlay for guidance towards "hotspots" of fibrosis and inflammation.
measure: Radiation exposure
time frame: At the end of each catheterization procedure through study completion,up to 5 years
description: To compare radiation exposure in this cohort of subjects (pre and post heart transplant) with recent historical controls undergoing matched invasive cardiology procedures at Children's National Medical Center prior to use of MR-guided cardiac catheterization.
5cc of blood will be collected if subject consent to the optional study. This blood will be
      used to identify serum biomarkers, and to validate the potential use for diagnostic purposes.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Months
maximum age: N/A
healthy volunteers: No
last name: Laura Olivieri, MD
role: Principal Investigator
affiliation: Children's National
last name: Laura Olivieri, MD
phone: 202-476-2020
email: lolivieri@childrensnational.org
last name: Joshua Kanter, MD
phone: 202-476-2020
email: jkanter@childrensnational.org
facility: 
status: Recruiting
country: United States
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responsible party type: Sponsor-Investigator
investigator affiliation: Children's National Research Institute
investigator full name: Laura Olivieri
investigator title: Associate Professor of Pediatrics/Cardiologist
mesh term: Cardiomyopathies
mesh term: Heart Defects, Congenital