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

Multi-Disciplinary Study: Magnetic Resonance, Histologic And Electron Microscopy Imaging Of Intravenous Superparamagnetic Crystalline Particles (Ferumoxytol) In CNS Inflammation

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.

Study Overview

• Status: Terminated
• Conditions: Nervous System Diseases; Diagnostic Imaging
• Intervention / Treatment: Drug: Ferumoxytol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inflammatory lesions; Subjects with dural, central nervous system (CNS) parenchymal based inflammatory, vascular or demyelinating lesions.	Drug: Ferumoxytol; 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); Other Names: Feraheme
Active Comparator: Vascular lesions; subjects will include those with vascular CNS lesions such as ischemic stroke, transient ischemic attack (TIA) with suspected carotid embolic origin, or vasculopathy involving the carotids, (including diagnosed carotid stenosis >50%) the aorta, or the arteries of the extremities, or diagnosed thrombosis of the intraabdominal, pelvic or extremity veins.	Drug: Ferumoxytol; 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); Other Names: Feraheme
Active Comparator: Lymph nodes; Subjects with enlarged cervical lymph nodes in which inflammatory processes (reactive lymph nodes) is part of the differentials.	Drug: Ferumoxytol; 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); Other Names: Feraheme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Lesions		72 hours
Degree of Contrast Enhancement	Scoring system for parameters: Degree of contrast enhancement (1=none, 2=moderate, 3=good, 4=excellent)	72 hours
Assessment of Border Delineation	The scoring parameters were: (1=none, 2=moderate, 3=good, 4=excellent).	72hrs
Internal Morphology of Lesions	The scoring parameters were: (1=poor, 2=moderate, 3=good).	72hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ferumoxytol Particles With Histology and Electron Microscopy in Biopsy Samples		72 hours
Side Effects/Safety of Ferumoxytol When Given During MRI.	Number of serious adverse events attributable to ferumoxytol.	30 days
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

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Edward A Neuwelt, MD, Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2004
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: April 10, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimated): April 16, 2008

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ferumoxytol
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Nervous System Diseases; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: OHSU-1562; 5R01NS034608 (U.S. NIH Grant/Contract)