Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance
Study Details
Study Description
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 |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| 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 Names:
Other: MRI-GE Healthcare 3 Tesla magnet
All patients will undergo
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps [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
- Correlation of Cell-bound Iron Quantities on QSM Sequences With Macrophage and Iron Stains on Histopathology [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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lucile Packard Children's Hospital | Stanford | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
- Lucile Packard Children's Hospital
Investigators
- Principal Investigator: Heike E Daldrup-Link, MD, PhD, Stanford University
Study Documents (Full-Text)
More Information
Publications
None provided.- 94027
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Feraheme |
|---|---|
| Arm/Group Description | Intravenous injection of Feraheme, 5 mg Fe/kg Interventions: Drug: Feraheme Procedure: MR Scan Feraheme: Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging MRI-GE Healthcare 3 Tesla magnet: All patients will undergo |
| Period Title: Overall Study | |
| STARTED | 21 |
| MR Imaging | 19 |
| COMPLETED | 19 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Feraheme |
|---|---|
| Arm/Group Description | Intravenous injection of Feraheme, 5 mg Fe/kg Interventions: Drug: Feraheme Procedure: MR Scan Feraheme: Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging MRI-GE Healthcare 3 Tesla magnet: All patients will undergo |
| Overall Participants | 21 |
| Age (Count of Participants) | |
| <=18 years |
14
66.7%
|
| Between 18 and 65 years |
7
33.3%
|
| >=65 years |
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
17.8
(2.8)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
9
42.9%
|
| Male |
12
57.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
9
42.9%
|
| Not Hispanic or Latino |
12
57.1%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
2
9.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
14.3%
|
| White |
15
71.4%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
1
4.8%
|
| Region of Enrollment (participants) [Number] | |
| United States |
21
100%
|
| Number of Patients with Kidney Transplant (Count of Participants) | |
| Count of Participants [Participants] |
21
100%
|
| MRI Compatibility (Count of Participants) | |
| Count of Participants [Participants] |
21
100%
|
| Drug allergies, specifically against iron compounds (Count of Participants) | |
| Count of Participants [Participants] |
0
0%
|
| GFR (ml/min/1.73 m2) [Mean (Standard Deviation) ] | |
| Rejection |
52
(24)
|
| Normal |
90
(29)
|
| Pregnancy (Count of Participants) | |
| Count of Participants [Participants] |
0
0%
|
Outcome Measures
| Title | Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps |
|---|---|
| Description | 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. |
| Time Frame | 24 hours to 7 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| T2* value of transplant kidney |
| Arm/Group Title | Feraheme |
|---|---|
| Arm/Group Description | Intravenous injection of Feraheme, 5 mg Fe/kg Interventions: Drug: Feraheme Procedure: MR Scan Feraheme: Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging MRI-GE Healthcare 3 Tesla magnet: All patients will undergo |
| Measure Participants | 19 |
| Rejection |
31.1
(14.4)
|
| No Rejection |
23.3
(5.4)
|
| Title | Correlation of Cell-bound Iron Quantities on QSM Sequences With Macrophage and Iron Stains on Histopathology |
|---|---|
| Description | 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. |
| Time Frame | 3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| CD163 positive macrophages |
| Arm/Group Title | Feraheme |
|---|---|
| Arm/Group Description | Intravenous injection of Feraheme, 5 mg Fe/kg Interventions: Drug: Feraheme Procedure: MR Scan Feraheme: Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging MRI-GE Healthcare 3 Tesla magnet: All patients will undergo |
| Measure Participants | 19 |
| Number [correlation coefficient] |
0
|
Adverse Events
| Time Frame | Continuously for 30 minutes and on study completion. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Feraheme | |
| Arm/Group Description | Intravenous injection of Feraheme, 5 mg Fe/kg Interventions: Drug: Feraheme Procedure: MR Scan Feraheme: Therapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging MRI-GE Healthcare 3 Tesla magnet: All patients will undergo | |
All Cause Mortality |
||
| Feraheme | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/21 (0%) | |
Serious Adverse Events |
||
| Feraheme | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/21 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Feraheme | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/21 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Heike E. Daldrup-Link |
|---|---|
| Organization | Stanford University, Department of Radiology |
| Phone | 650-497-8601 |
| emisquez@stanford.edu |
- 94027