Clincosm LogoSign in Get a demo

MRI to Predict Rejection and Failure in Transplant and Cardiomyopathy Patients

Sponsor
Laura Olivieri (Other)
Overall Status
Recruiting
CT.gov ID
NCT03822442
Collaborator
(none)
200
Enrollment
1
Location
62
Anticipated Duration (Months)
3.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    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

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    200 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    MRI to Predict Rejection and Failure in Transplant and Cardiomyopathy Patients
    Actual Study Start Date :
    Nov 1, 2019
    Anticipated Primary Completion Date :
    Dec 31, 2024
    Anticipated Study Completion Date :
    Dec 31, 2024

    Outcome Measures

    Primary Outcome Measures

    1. Correlate MRI imaging results to biopsy results Correlate MRI imaging with endomyocardial biopsy [At the end of each catheterization procedure through study completion,up to 5 years]

      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.

    Secondary Outcome Measures

    1. Compare yield of biopsy specimen collection using x-ray vs x-ray fused MRI images [At the end of each catheterization procedure through study completion,up to 5 years]

      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.

    2. Radiation exposure [At the end of each catheterization procedure through study completion,up to 5 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Children and adults of any age with heart transplant, suspected or confirmed cardiomyopathy

    • Undergoing clinically-indicated ("medically necessary") cardiovascular catheterization

    Exclusion Criteria:

    • Cardiovascular instability including hemodynamic instability (such as requiring significant vasoactive infusion support) or mechanical hemodynamic support.

    • Women who are pregnant

    • Women who are nursing and who do not plan to discard breast milk for 24 hours

    • Exclusion criteria for MRI

    • Central nervous system aneurysm clips

    • Implanted neural stimulator

    • Implanted cardiac pacemaker or defibrillator which are not MR safe or MR conditional according to the manufacturer

    • Cochlear implant

    • Ocular foreign body (e.g. metal shavings)

    • Implanted Insulin pump

    • Metal shrapnel or bullet.

    • Exclusion criteria for Gadolinium

    • Renal disease with estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73 m2 body surface area

    The eGFR will be used to estimate renal function if reported by the laboratory.

    The Schwartz equation 33 for estimation of GFR in children as recommended by the NKDEP is as follows:

    GFR (mL/min/1.73 m2) = (k × height) / serum creatinine concentration

    where k = constant defined as follows: k = 0.33 in premature infants k = 0.45 in term infants to 1 year of age k = 0.55 in children to 13 years of age k = 0.70 in adolescent males (not females because of the presumed increase in male muscle mass, the constant remains 0.55 for females) Height in cm Serum creatinine in mg/dL

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's National Health System Washington District of Columbia United States 20010

    Sponsors and Collaborators

    • Laura Olivieri

    Investigators

    • Principal Investigator: Laura Olivieri, MD, Children's National

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Laura Olivieri, Associate Professor of Pediatrics/Cardiologist, Children's National Research Institute
    ClinicalTrials.gov Identifier:
    NCT03822442
    Other Study ID Numbers:
    • 11408
    First Posted:
    Jan 30, 2019
    Last Update Posted:
    Jul 22, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Laura Olivieri, Associate Professor of Pediatrics/Cardiologist, Children's National Research Institute
    Cardiomyopathy, cardiomegaly
    cardiac transplant
    Additional relevant MeSH terms:
    Cardiomyopathies
    Heart Defects, Congenital

    Study Results

    No Results Posted as of Jul 22, 2022