Osteonecrosis
Conditions
Brief summary
The goal of the project is to evaluate osteonecrosis before and after decompression surgery with ferumoxytol-enhanced MRI.
Detailed description
The goal of the project is to evaluate osteonecrosis before and after decompression surgery with ferumoxytol-enhanced MRI. The investigators approach relies on the FDA-approved iron supplement ferumoxytol (Feraheme), which is used off label as a contrast agent for MRI. Ferumoxytol is composed of iron oxide nanoparticles, which provide a strong T1- and T2-signal on magnetic resonance (MR) images and are taken up by cells in bone marrow. 20 patients will undergo MRI before and after decompression surgery and transplantation of bone marrow derived cells. 10 patients will receive a single intravenous injection of ferumoxytol prior to their surgery. 10 additional patients will serve as untreated controls. The investigators hypothesize that MR images after intravenous injection of ferumoxytol will improve lesion detection and allow to track transplanted bone marrow cells. MR imaging findings will be correlated with clinical outcomes.
Interventions
DRUGFerumoxytol-enhanced magnetic resonance imaging
Eligible patients receive a single ferumoxytol-dose and follow-up magnetic resonance imaging to evaluate success of stem cell transplant
DEVICEMagentic Resonance Imaging
Both arms will receive MRI
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Osteonecrosis * planned decompression surgery with autologous stem cell transplant
Exclusion criteria
* Contraindications for magnetic resonance imaging * Hemosiderosis/hemochromatosis ( patients can still be included in the non-ferumoxytol arm)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Signal to Noise Ratio (SNR) | week 1 postsurgery | SNR is a measurement that compares the strength of a signal to the level of background noise. It is often expressed in decibels (dB) and is calculated by dividing the signal power by the noise power. A ratio greater than 1:1 indicates that there is more signal than noise. First, for each lesion the MR signal intensity (SI) of the lesion and the SI of the background (= noise in the image) was measured, then the SI of the lesion was divided by the SI of the noise to obtain the signal to noise ratio. Then, the mean SNR and standard deviation was calculated for the different groups of lesions and compared to the mean SNR between treated versus not treated lesions and treated lesions at different time points after the treatment using statistical tests. |
| T2*-Relaxation Time | week 1 postsurgery | T2\* relaxation time is a measure of how quickly transverse magnetization decays in magnetic resonance imaging (MRI). It's a key factor in image contrast in gradient-echo (GRE) sequences and is used in many MRI applications, such as perfusion imaging, susceptibility-weighted imaging, and functional imaging. Lower T2\* relaxation times indicate greater contrast agent uptake in cells. |
| Evaluation of Treatment Response to Decompression Surgery and Stem Cell Transplant | one year | Number of femurs that did not collapse by 1 year follow up. Evaluation of progression of osteonecrosis via scale 1-4, bone marrow edema, collapse of subchondral fractures. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol-enhanced MRI Patients scheduled for routine decompression surgery and autologous stem cell transplant receive ferumoxytol injection (Feraheme, AMAG, 5mg Fe/kg, single administration), and follow-up magnetic resonance imaging in regular intervals for evaluation of the response to treatment. | 9 |
| Non-ferumoxytol Enhanced MRI Patients scheduled for routine decompression surgery and autologous stem cell transplant receive follow-up magnetic resonance imaging in regular intervals for evaluation of the response to treatment. | 5 |
| Total | 14 |
Baseline characteristics
| Characteristic | Ferumoxytol-enhanced MRI | Non-ferumoxytol Enhanced MRI | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 5 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 0 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 6 Participants |
| Region of Enrollment United States | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 |
| other Total, other adverse events | 0 / 9 | 0 / 5 |
| serious Total, serious adverse events | 0 / 9 | 0 / 5 |
Outcome results
Primary
Evaluation of Treatment Response to Decompression Surgery and Stem Cell Transplant
Number of femurs that did not collapse by 1 year follow up. Evaluation of progression of osteonecrosis via scale 1-4, bone marrow edema, collapse of subchondral fractures.
Time frame: one year
Population: Long-term follow up was conducted in the ferumoxytol group only
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Ferumoxytol-enhanced MRI | Evaluation of Treatment Response to Decompression Surgery and Stem Cell Transplant | 12 Femur |
Primary
Signal to Noise Ratio (SNR)
SNR is a measurement that compares the strength of a signal to the level of background noise. It is often expressed in decibels (dB) and is calculated by dividing the signal power by the noise power. A ratio greater than 1:1 indicates that there is more signal than noise. First, for each lesion the MR signal intensity (SI) of the lesion and the SI of the background (= noise in the image) was measured, then the SI of the lesion was divided by the SI of the noise to obtain the signal to noise ratio. Then, the mean SNR and standard deviation was calculated for the different groups of lesions and compared to the mean SNR between treated versus not treated lesions and treated lesions at different time points after the treatment using statistical tests.
Time frame: week 1 postsurgery
Population: Participants who completed the protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol-enhanced MRI | Signal to Noise Ratio (SNR) | 33.82 dB | Standard Deviation 12.43 |
| Non-ferumoxytol Enhanced MRI | Signal to Noise Ratio (SNR) | 129.56 dB | Standard Deviation 10.93 |
p-value: 0.002Mixed Models Analysis
Primary
T2*-Relaxation Time
T2\* relaxation time is a measure of how quickly transverse magnetization decays in magnetic resonance imaging (MRI). It's a key factor in image contrast in gradient-echo (GRE) sequences and is used in many MRI applications, such as perfusion imaging, susceptibility-weighted imaging, and functional imaging. Lower T2\* relaxation times indicate greater contrast agent uptake in cells.
Time frame: week 1 postsurgery
Population: Participants who completed the protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol-enhanced MRI | T2*-Relaxation Time | 9.04 milliseconds | Standard Deviation 0.7 |
| Non-ferumoxytol Enhanced MRI | T2*-Relaxation Time | 13.7 milliseconds | Standard Deviation 2.5 |
p-value: 0.02Mixed Models Analysis