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Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance

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ClinicalTrials.gov Identifier: NCT02006108
Recruitment Status : Completed
First Posted : December 9, 2013
Results First Posted : June 27, 2017
Last Update Posted : May 11, 2018
Sponsor:
Collaborator:
Lucile Packard Children's Hospital
Information provided by (Responsible Party):
Heike E Daldrup-Link, Stanford University

Brief Summary:
The goal of this study is to develop a non-invasive imaging test for in vivo detection of kidney transplant rejection. The hypotheses are that 1) Ferumoxytol-MRI can generate accurate estimates of tissue iron concentrations and tissue macrophages. 2) The signal given by a renal allograft on Ferumoxytol-MRI demonstrates significant differences between rejected and non-rejected transplants.

Condition or disease Intervention/treatment Phase
Renal Transplant Rejection Drug: Feraheme Other: MRI-GE Healthcare 3 Tesla magnet Not Applicable

Detailed Description:

In children with kidney transplants, immunologically mediated rejection is the major cause of allograft failure. Thus, the therapeutic success of kidney transplants is highly dependent on the ability to avoid rejection during both the acute and chronic phase after transplantation. Children with kidney transplants currently undergo at least three routine (protocol) biopsies during the first two years after the transplantation in addition to biopsies required to investigate deterioration of kidney function. These biopsies are invasive and nearly always require general anesthesia, causing anxiety and distress of the patients and their parents, as well as significant costs to our health care system. There is currently no non-invasive diagnostic tool capable of detecting rejection in vivo. Thus, the goal of this study is to develop a non-invasive imaging test for in vivo detection of kidney transplant rejection. The investigators propose to accomplish this goal by detecting macrophage infiltration in kidney transplants with iron oxide nanoparticle-enhanced MR imaging. Macrophages play a major role in transplant rejection. CD68-positive macrophages comprise approximately 50% of the infiltrating leukocyte population in renal allograft rejection, they co-localize with areas of tissue-damage and fibrosis, and are preponderant in more severe forms of rejection. The investigators hypothesize that iron oxide nanoparticle-enhanced MR imaging can detect differences in macrophage infiltrations in renal allografts undergoing rejection as opposed to allografts without significant rejection. This hypothesis is based on the bio-physical properties of intravenously injected superparamagnetic iron oxide nanoparticles, which are phagocytosed by tissue macrophages and cause strong signal effects on MR images.

The specific aims of the study are the following:

Aim #1. Technical Development of a Quantitative Susceptibility Mapping (QSM)-Sequence for in vivo MRI detection and quantification of iron oxide nanoparticle-labeled macrophages.This aim will focus on the technical development of Quantitative Susceptibility Mapping (QSM), a novel MR imaging pulse sequence that will be used to accurately quantify the tissue concentration of free ferumoxytol and ferumoxytol in macrophages in renal allografts. Based on pulse sequence optimizations of phantoms with known concentrations of free and cell-bound iron, we expect to generate accurate estimates of tissue iron concentrations and macrophages with the QSM-MRI method.

Aim #2. Detect rejection in kidney allografts with ferumoxytol-enhanced MRI. The investigators hypothesize that ferumoxytol can detect and quantify macrophages in kidney allografts, based upon the observation that iron oxide nanoparticles can be taken up by macrophages in malignant tumors. The investigators will evaluate the ability of ferumoxytol to map macrophage quantities in renal allografts, with histopathological correlation. We expect significantly higher ferumoxytol-MRI enhancement and macrophage quantities in rejected allografts compared to non-rejected allografts.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Non-invasive MR Imaging Diagnosis of Transplant Rejection
Actual Study Start Date : November 27, 2012
Actual Primary Completion Date : April 11, 2017
Actual Study Completion Date : April 11, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Ferumoxytol

Arm Intervention/treatment
Experimental: Feraheme

Intravenous injection of Feraheme, 5 mg Fe/kg

Interventions:

Drug: Feraheme Procedure: MR Scan

Drug: Feraheme
Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging
Other Name: Ferumoxytol

Other: MRI-GE Healthcare 3 Tesla magnet
All patients will undergo
Other Names:
  • Magnetic Resonance Imaging
  • MR Imaging




Primary Outcome Measures :
  1. Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps [ Time Frame: 24 hours to 7 days ]
    According to the study hypothesis, macrophage infiltration into rejected kidneys will be significantly greater than in healthy kidneys; since macrophages are expected to phagocytose injected iron, there should be a detectable difference in signal intensity between healthy and rejected organs. This can be evaluated using semiquantitative T2* maps.


Secondary Outcome Measures :
  1. Correlation of Cell-bound Iron Quantities on QSM Sequences With Macrophage and Iron Stains on Histopathology [ Time Frame: 3 weeks ]
    To evaluate our ability to quantify cell-bound iron using the novel QSM sequence, we use histopathological data showing 1) the iron content of renal tissue sampled, and 2) the level of macrophage infiltration of the renal tissue. We will perform iron and macrophage stains in biopsy tissues in order to determine this.



Information from the National Library of Medicine

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Ages Eligible for Study:   8 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Completed solid organ transplant with referral for transplant follow-up

Exclusion Criteria:

  • Exclusion criteria comprise MR-incompatible metal implants, need of sedation (since an anesthesia is not supported by this), claustrophobia or hemosiderosis/hemochromatosis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02006108


Locations
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United States, California
Lucile Packard Children's Hospital
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Lucile Packard Children's Hospital
Investigators
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Principal Investigator: Heike E Daldrup-Link, MD, PhD Stanford University
  Study Documents (Full-Text)

Documents provided by Heike E Daldrup-Link, Stanford University:
Study Protocol  [PDF] November 30, 2016
Statistical Analysis Plan  [PDF] April 6, 2018

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Responsible Party: Heike E Daldrup-Link, Principle Investigator, Stanford University
ClinicalTrials.gov Identifier: NCT02006108    
Other Study ID Numbers: 94027
First Posted: December 9, 2013    Key Record Dates
Results First Posted: June 27, 2017
Last Update Posted: May 11, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Heike E Daldrup-Link, Stanford University:
kidney
transplant
rejection
Feraheme
ferumoxytol
Additional relevant MeSH terms:
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Ferrosoferric Oxide
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions