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

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Diagnostic
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2020

Interventions

  • 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)

Arms, Groups and Cohorts

  • Active Comparator: Inflammatory lesions
    • Subjects with dural, central nervous system (CNS) parenchymal based inflammatory, vascular or demyelinating lesions.
  • 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.
  • Active Comparator: Lymph nodes
    • Subjects with enlarged cervical lymph nodes in which inflammatory processes (reactive lymph nodes) is part of the differentials.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • Ferumoxytol Particles With Histology and Electron Microscopy in Biopsy Samples
    • Time Frame: 72 hours
  • Side Effects/Safety of Ferumoxytol When Given During MRI.
    • Time Frame: 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
    • Time Frame: 6 months

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Oregon Health and Science University
  • Collaborator
    • National Institute of Neurological Disorders and Stroke (NINDS)
  • Provider of Information About this Clinical Study
    • Principal Investigator: Edward Neuwelt, Professor – Oregon Health and Science University
  • Overall Official(s)
    • Edward A Neuwelt, MD, Principal Investigator, Oregon Health and Science University

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