MR, Histologic And EM Imaging Of Intravenous Ferumoxytol In Central Nervous System (CNS) Inflammation

Study Overview
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Brief Summary
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The purpose of this study is to address safety and efficiency of a new iron particle contrast agent, ferumoxytol. This product may be more useful in viewing the vessels of the brain and areas in the brain on magnetic resonance imaging (MRI), or magnetic resonance angiography (MRA), than the standard substance, gadolinium, injected during MRI and MRA. Other ways in which ferumoxytol may help include the following: Ferumoxytol may provide the ability to better see inflammatory lesions on magnetic resonance imaging (MRI) scans Ferumoxytol may be useful in its ability to cross blood vessels into inflammatory processes, and Ferumoxytol, because of its size and ability to get into the area next to your inflammatory lesion and could assist in the treatment of inflammatory lesions association with cardiac surgery or CNS vascular surgery.

Detailed Description
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Subjects are recruited as patients in one of the neurology, neurosurgery, neuro-oncology, Multiple Sclerosis Clinic or cardiothoracic surgery clinics at OHSU. Eligible subjects will be enrolled in different groups based on their disease (MS, cardiac surgery or CNS vascular surgery, stroke). Subsequently a MRI and MRA of the brain using the standard contrast agent (Gadolinium) will be obtained; this study will be compared with the ferumoxytol-contrasted MRA and MRIs performed the next day(s). Visit 1: the subjects are enrolled and distributed in their corresponding group; also basic laboratory studies are obtained as well as a Gadolinium contrasted MRI and MRA of the brain. For Groups 1 and 2 (MS and Stroke): Visit 2: Ferumoxytol will be injected as an i.v. bolus. The total dose over 2 hours will not exceed 510mg, and can be divided into multiple smaller doses such as 1 mg Fe/kg to optimize MRA imaging and may be diluted up to 4 fold in normal saline to reduce T2* effects in the MR angiography. Visit 3: 24 hours after the second visit an MRI with the standard contrast agent will be done. Last visit: 1 month after Ferumoxytol administration, the subject will be reassessed with physical and laboratory exams. For Groups 3 and 4 (Cardiac surgery or CNS vascular surgery): After the screening visit (Visit 1) and baseline MRI and MRA you will be randomly assigned to one of two groups. These groups are very similar but there are slight differences in the schedule of events. Group 3a and 4a: ferumoxytol infusion (Visit 2) before surgery Group 3b and 4b: ferumoxytol infusion (Visit 2) after surgery Visit 2: Ferumoxytol will be injected as an i.v. bolus. The total dose over 2 hours will not exceed 510mg, and can be divided into multiple smaller doses such as 1 mg Fe/kg to optimize MRA imaging and may be diluted up to 4 fold in normal saline to reduce T2* effects in the MR angiography. Visit 3: 24-72 hours after the second visit an MRI with the standard contrast agent will be done. Last visit: 1 month after Ferumoxytol administration, the subject will be reassessed with physical and laboratory exams.

Official Title
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Multi-Disciplinary Study: MR, Histologic And EM Imaging Of Intravenous Superparamagnetic Crystalline Particles (Ferumoxytol) In CNS Inflammation

Conditions
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Nervous System Diseases, Diagnostic Imaging

Intervention / Treatment
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* Drug: Ferumoxytol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have a clinical, radiological or established histological diagnosis of multiple sclerosis, stroke, or be requiring cardiac or CNS vascular surgery. Subjects with a CNS inflammatory lesion that is suspicious for neoplasm or radiation induced inflammation (vasculitis) will also be included (group 1a). McDonald's criteria will be used for the diagnosis of multiple sclerosis. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Subjects with MS or any other inflammatory process | Drug: Ferumoxytol<br>* 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)<br>* Other names: Feraheme;|
| Active Comparator: 2<br>Subjects with stroke | Drug: Ferumoxytol<br>* 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)<br>* Other names: Feraheme;|
| Active Comparator: 3<br>Subjects receive ferumoxytol before cardiac surgery or CNS vascular surgery | Drug: Ferumoxytol<br>* 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)<br>* Other names: Feraheme;|
| Active Comparator: 4<br>Subjects receive ferumoxytol after cardiac surgery or CNS vascular surgery | Drug: Ferumoxytol<br>* 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)<br>* Other names: Feraheme;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety of ferumoxytol. |  | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare ferumoxytol MR with the gold standard gadolinium enhanced MR in adults with CNS inflammatory or demyelinating brain disease (multiple sclerosis) or related diseases such a as ADEM. |  | 72 hours | 
| To compare ferumoxytol MR with the gold standard gadolinium enhanced MR in adults with ischemic processes, stroke, or undergoing CNS vascular surgery (carotid stenting or carotid endarterectomy). |  | 72 hours | 
| To identify inflammatory and embolic lesions in the brains of patients undergoing cardiac surgery with and without cardiopulmonary bypass utilizing ferumoxytol enhanced MRI. |  | 72 hours | 
| To evaluate the use of ferumoxytol MRA to image the vascular bed of CNS inflammatory and ischemic lesions. |  | 72 hours | 
| To evaluate the utility of ferumoxytol to differentiate between inflammatory and neoplastic lesions. |  | 72 hours | 
| To localize ferumoxytol particles with histology and electron microscopy in biopsy samples in which the diagnosis is unclear and biopsy is needed to exclude lymphoma or other alternative diagnosis and compare with imaging results. |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ferumoxytol