Diagnostic Imaging, Nervous System Diseases
Conditions
Keywords
ferumoxytol
Brief summary
This exploratory study utilizes ferumoxytol, an iron oxide nanoparticle MR contrast agent for imaging various inflammatory processes in the head and neck region, spine, including the central nervous system. The protocol enrolls subjects with radiological or histological diagnosis of unknown, dural, or parenchymal CNS lesions, multiple sclerosis, TIA or stroke, vasculitis, or other vascular lesions; arterial vasculopathy and venous thrombosis; or enlarged cervical lymph nodes. The main purpose of this study is to better understand the underlying cellular mechanisms, contrast agent extravasation, uptake into macrophages and to assess its value in clinical MR imaging.
Interventions
DRUGFerumoxytol
Ferumoxytol will be injected as i.v. bolus(es) at 3ml/s followed by a saline flush. The maximum total dose over 30 to 60 minutes will be 510mg Fe. Separate boluses will be used for perfusion MR and MRA. Ferumoxytol may be diluted up to 28 fold in normal saline to reduce T2\* effects in the MR angiography. Rate of administration can be varied based on the subject's iv site, but will never exceed 510mg Fe /17s (as was done in phaseIII trials)
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Oregon Health and Science University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a clinical, radiological or established histological diagnosis of dural or central nervous system (CNS) parenchymal based inflammatory, vascular or demyelinating lesions, radiological suspected diagnosis of vascular CNS lesions such as ischemic stroke, TIA with suspected carotid embolic origin, or vasculopathy involving the carotids (including diagnosed carotid stenosis \>50%), the aorta, the arteries of the extremities, or diagnosed thrombosis of the intraabdominal, pelvic or extremity veins, or clinical or radiological diagnosis of enlarged cervical lymph nodes in which inflammatory processes (reactive lymph nodes) is part of the differentials. * Subjects must be 18 years or older * Subjects will be followed for at least 1 month after the infusion of ferumoxytol. * All subjects or their authorized representative must sign a written informed consent and give HIPAA authorization in accordance with institutional guidelines. * Female subjects of child-bearing potential must be postmenopausal, surgically sterile, or using a reliable form of contraception for at least a month. These criteria can be waved at the discretion of the investigator if the one-month wait required is not in the best interest of the patient. * Karnofsky must be 30% or greater
Exclusion criteria
* Subjects with clinically significant signs of uncal herniation * Subjects who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to Gd contrast material. * Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations * Subjects with known hepatic insufficiency or cirrhosis * Subjects with known or suspected iron overload * HIV-positive subjects on combination anti-retroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ferumoxytol * Pregnant or lactating women are excluded from this study because of possible risk to the fetus or infant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Lesions | 72 hours | — |
| Degree of Contrast Enhancement | 72 hours | Scoring system for parameters: Degree of contrast enhancement (1=none, 2=moderate, 3=good, 4=excellent) |
| Assessment of Border Delineation | 72hrs | The scoring parameters were: (1=none, 2=moderate, 3=good, 4=excellent). |
| Internal Morphology of Lesions | 72hrs | The scoring parameters were: (1=poor, 2=moderate, 3=good). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side Effects/Safety of Ferumoxytol When Given During MRI. | 30 days | Number of serious adverse events attributable to ferumoxytol. |
| Iron Uptake and Clearance in Abdominal Organs, Such as the Liver, Spleen, Pancreas and Bone Marrow by Applying Usual Abdominal MR Sequences at Multiple Time Points | 6 months | — |
| Ferumoxytol Particles With Histology and Electron Microscopy in Biopsy Samples | 72 hours | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Inflammatory Lesions Subjects with dural, central nervous system (CNS) parenchymal based inflammatory, vascular or demyelinating lesions. | 230 |
| Group 2: Vascular Lesions Subjects will include those with vascular CNS lesions such as ischemic stroke, TIA with suspected carotid embolic origin, or atherosclerotic or inflammatory vasculopathy involving the carotids (including diagnosed carotid stenosis \>50%), aorta and the arteries of the extremities or thrombosis of the intraabdominal, pelvic or extremity veins. | 25 |
| Group 3: Lymph Nodes Subjects with enlarged cervical lymph nodes in which inflammatory processes (reactive lymph nodes) is part of the differentials. | 0 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 12 | 2 | 0 |
Baseline characteristics
| Characteristic | Group 1: Inflammatory Lesions | Group 2: Vascular Lesions | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 46 Participants | 1 Participants | 47 Participants |
| Age, Categorical Between 18 and 65 years | 184 Participants | 24 Participants | 208 Participants |
| Age, Continuous | 51.6 years STANDARD_DEVIATION 15.8 | 61.4 years STANDARD_DEVIATION 9.6 | 52.3 years STANDARD_DEVIATION 15.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 1 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 213 Participants | 24 Participants | 237 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 213 Participants | 25 Participants | 238 Participants |
| Region of Enrollment United States | 230 participants | 25 participants | 255 participants |
| Sex: Female, Male Female | 105 Participants | 14 Participants | 119 Participants |
| Sex: Female, Male Male | 125 Participants | 11 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 218 | 0 / 23 | 0 / 0 |
| other Total, other adverse events | 11 / 218 | 2 / 23 | 0 / 0 |
| serious Total, serious adverse events | 39 / 218 | 2 / 23 | 0 / 0 |
Outcome results
Primary
Assessment of Border Delineation
The scoring parameters were: (1=none, 2=moderate, 3=good, 4=excellent).
Time frame: 72hrs
Population: Due to the study closing prematurely, the images for the 23 subjects in group 2 were collected but not processed for analysis, and no data were collected in group 3 for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inflammatory Lesions | Assessment of Border Delineation | Gadolinium | 3.2 Score assessment of border delineation | Standard Deviation 0.87 |
| Group 1: Inflammatory Lesions | Assessment of Border Delineation | Ferumoxtyol | 3.2 Score assessment of border delineation | Standard Deviation 0.75 |
Primary
Degree of Contrast Enhancement
Scoring system for parameters: Degree of contrast enhancement (1=none, 2=moderate, 3=good, 4=excellent)
Time frame: 72 hours
Population: Due to the study closing prematurely, the images for the 23 subjects in group 2 were collected but not processed for analysis, and no data were collected in group 3 for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inflammatory Lesions | Degree of Contrast Enhancement | Gadolinium | 2.9 Score of contrast enhancement | Standard Deviation 1.13 |
| Group 1: Inflammatory Lesions | Degree of Contrast Enhancement | Ferumoxytol | 2.7 Score of contrast enhancement | Standard Deviation 1.13 |
Primary
Internal Morphology of Lesions
The scoring parameters were: (1=poor, 2=moderate, 3=good).
Time frame: 72hrs
Population: Due to the study closing prematurely, the images for the 23 subjects in group 2 were collected but not processed for analysis, and no data were collected in group 3 for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inflammatory Lesions | Internal Morphology of Lesions | Gadolinium | 2.4 Score of internal morphology of lesions | Standard Deviation 1.04 |
| Group 1: Inflammatory Lesions | Internal Morphology of Lesions | Ferumoxytol | 2.5 Score of internal morphology of lesions | Standard Deviation 0.99 |
Primary
Number of Lesions
Time frame: 72 hours
Population: Due to the study closing prematurely, the images for the 23 subjects in group 2 were collected but not processed for analysis, and no data were collected in group 3 for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Inflammatory Lesions | Number of Lesions | Gadolinium | 1.8 Number of lesions | Standard Deviation 1.17 |
| Group 1: Inflammatory Lesions | Number of Lesions | Ferumoxytol | 1.9 Number of lesions | Standard Deviation 1.09 |
Secondary
Ferumoxytol Particles With Histology and Electron Microscopy in Biopsy Samples
Time frame: 72 hours
Population: Due to the study closing prematurely, we did not collect these data.
Secondary
Iron Uptake and Clearance in Abdominal Organs, Such as the Liver, Spleen, Pancreas and Bone Marrow by Applying Usual Abdominal MR Sequences at Multiple Time Points
Time frame: 6 months
Population: Due to the study closing prematurely, we did not enroll any subjects into this subgroup nor gather any data.
Secondary
Side Effects/Safety of Ferumoxytol When Given During MRI.
Number of serious adverse events attributable to ferumoxytol.
Time frame: 30 days
Population: Of the 230 subjects enrolled in group 1, 12 withdrew or were taken of study prior to receiving ferumoxytol. The 218 subjects remaining were analyzed. Of the 25 subjects enrolled in group 2, 2 withdrew or were taken of study prior to receiving ferumoxyotol. The 23 subjects remaining were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Inflammatory Lesions | Side Effects/Safety of Ferumoxytol When Given During MRI. | 1 Number of serious AEs attributable to Fe |
| Group 2: Vascular Lesions | Side Effects/Safety of Ferumoxytol When Given During MRI. | 0 Number of serious AEs attributable to Fe |