Renal Transplant RejectionNCT02006108
Imaging Kidney Transplant Rejection Using Ferumoxytol-Enhanced Magnetic Resonance
A study testing Feraheme and MRI-GE Healthcare 3 Tesla magnet in people with Renal Transplant Rejection, run by Stanford University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Transplant Rejection
- What is being tested?
- Feraheme and MRI-GE Healthcare 3 Tesla magnet
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Nov 2012to 11 Apr 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Completed solid organ transplant with referral for transplant follow-up
Who cannot join
- Exclusion criteria comprise MR-incompatible metal implants, need of sedation (since an anesthesia is not supported by this), claustrophobia or hemosiderosis/hemochromatosis.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lucile Packard Children's Hospital
Stanford, California, 94305
About this study
Official title: Non-invasive MR Imaging Diagnosis of Transplant Rejection
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.
Read the 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.
- Conditions
- Renal Transplant Rejection
- Being tested
- Feraheme, MRI-GE Healthcare 3 Tesla magnet
- Keywords
- kidney, transplant, rejection, Feraheme, ferumoxytol
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FerahemeDrug
Also called Ferumoxytol
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 magnetOther
Also called Magnetic Resonance Imaging, MR Imaging
All patients will undergo
| Study group | Role | What they receive |
|---|---|---|
| Feraheme | Experimental | Intravenous injection of Feraheme, 5 mg Fe/kg
Interventions:
Drug: Feraheme Procedure: MR Scan Receives: Drug: Feraheme; Other: MRI-GE Healthcare 3 Tesla magnet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps
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.
Measured: 24 hours to 7 days
Secondary outcomes (1)
Correlation of Cell-bound Iron Quantities on QSM Sequences With Macrophage and Iron Stains on Histopathology
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.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2013 (estimated)
- Study start27 Nov 2012
- Primary completion11 Apr 2017
- Study completion11 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Lucile Packard Children's Hospital
- Responsible party
- Principal investigator, Heike E Daldrup-Link, Stanford University
- Investigators
- Heike E Daldrup-Link, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02006108
- Sponsor's protocol ID
- 94027
- Status last verified
- Apr 2018
- First submitted
- 28 Oct 2013
- Last updated
- 11 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive MR Imaging Diagnosis of Transplant Rejection
- ClinicalTrials.gov ID
- NCT02006108
- Acronym / sponsor ID
- 94027
- Conditions
- Renal Transplant Rejection
- Keywords
- kidney, transplant, rejection, Feraheme, ferumoxytol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Lucile Packard Children's Hospital
- Study start
- 27 Nov 2012 (actual)
- Primary completion
- 11 Apr 2017 (actual)
- Study completion
- 11 Apr 2017 (actual)
- First posted
- 9 Dec 2013 (estimated)
- Results
- Posted 27 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Feraheme | Experimental | Drug: Feraheme, Other: MRI-GE Healthcare 3 Tesla magnetIntravenous injection of Feraheme, 5 mg Fe/kg Interventions: Drug: Feraheme Procedure: MR Scan |
Who may qualify
- Ages
- 8 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Completed solid organ transplant with referral for transplant follow-up
Key exclusion criteria (1 listed)
- Exclusion criteria comprise MR-incompatible metal implants, need of sedation (since an anesthesia is not supported by this), claustrophobia or hemosiderosis/hemochromatosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FerahemeAlso: FerumoxytolTherapeutic classification: iron preparations. Use: Off-label use of ultrasmall paramagnetic iron nanoparticle as contrast agent for magnetic resonance imaging | Drug | Feraheme |
| MRI-GE Healthcare 3 Tesla magnetAlso: Magnetic Resonance Imaging, MR ImagingAll patients will undergo | Other | Feraheme |
Primary outcome
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.
1 secondary outcome
Correlation of Cell-bound Iron Quantities on QSM Sequences With Macrophage and Iron Stains on Histopathology
Time frame: 3 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Renal Transplant Rejection
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
Not yet recruitingPhase 2
(TNX-1500) in Kidney Transplant Recipients
Kidney Transplant, Kidney Transplant Failure and Rejection
RecruitingPhase 2
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
Microvascular Inflammation
Not yet recruitingObservational study
Assessment of Perceived Stress in an Observational Study Evaluating a Biopsy-sparing Surveillance Strategy in Kidney Transplant Recipients With Blood and Urinary Biomarkers Predictive of the Absence of Rejection
Renal Transplantation; Complication, Renal Transplant
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Heike E Daldrup-Link, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Feraheme and MRI-GE Healthcare 3 Tesla magnet in people with Renal Transplant Rejection, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiologically Detectable Differences in Signal Intensity Between Healthy and Rejected Kidneys, Measured Using T2* Maps (time frame: 24 hours to 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2018.