In Vivo Characterization of Inflammation With Ferumoxytol, an Ultrasmall Superparamagnetic Iron Oxide Nanoparticle, on 7 Tesla Magnetic Resonance Imaging
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis; Inflammation
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Contrast agents help things show up better on magnetic resonance imaging (MRI) scans.
      Researchers want to see if the drug ferumoxytol is a good contrast agent. They want to
      determine that it does not cause prolonged MRI changes in the brain and to see if it helps
      identify inflammation in multiple sclerosis

      Objective:

      - To learn how ferumoxytol can be used to image inflammation in multiple sclerosis (MS).

      Eligibility:

        -  Adults ages 18 70 who have MS.

        -  Healthy volunteers ages 18 70.

      Design:

        -  Participants will have 5 clinic visits over 6 months.

        -  Participants will be screened with a medical history, neurological exam, and blood draw.
           Full clinical measures will be obtained.

        -  Participants will have a 7 tesla brain MRI scan that may include gadolinium contrast
           agent. The MRI is a metal cylinder in a strong magnetic field. The participant will lie
           on a table that can slide in and out of the cylinder.

        -  During visit 2, ferumoxytol with be given through a catheter (a thin plastic tube) that
           is inserted with a needle into a vessel in the arm.

      <TAB>- Participants will then have a 7 tesla MRI scan of the brain..

        -  At each of the next 3 clinic visits, participants will have a 7 tesla brain MRI and have
           blood drawn. The MRIs may include gadolinium.

        -  Participants may have a full neurologic exam at these visits. At the final visit, full
           clinical measures will be obtained.

        -  Participants may have more MRI scans if a 6-month MRI shows ferumoxytol still in the
           brain.
    

Detailed description: 
      Objective

      The goals of this pilot study are to (1) demonstrate the safety of ferumoxytol, a United
      States Food and Drug Administration (FDA) approved drug used in the treatment of iron
      deficiency anemia, as a contrast agent for brain magnetic resonance imaging (MRI), as
      determined by a lack of long-term signal change in healthy volunteers (HV) and people with
      multiple sclerosis (MS); (2) determine if ferumoxytol enhancement can be detected in MS
      lesions on 7-tesla (T) MRI; and (3) examine the spatial and temporal enhancement patterns of
      ferumoxytol compared to patterns seen with gradient-echo imaging and gadolinium contrast in
      MS lesions.

      Study population

      Up to 10 HVs and up to 10 participants with MS will be recruited for this study.

      Design

      Participants will undergo a series of brain MRIs on a 7 T scanner. MRI will be before
      (baseline) and 0-8 hours, 24-96 hours, 1 month, and 6 months following ferumoxytol
      administration.

      Outcome measures

      The primary outcome measure is change in gradient-echo T2-weighted signal (derived from an MR
      sequence sensitive to paramagnetic agents such as iron) in the globus pallidus, a known brain
      iron reservoir, 6 months following ferumoxytol administration. Thus, we will determine if
      ferumoxytol induces long-lasting brain signal intensity changes in HV and MS. Secondary
      outcome measures are: (1) the number, location, and qualitative morphology of ferumoxytol,
      gradient-echo phase, and gadolinium-enhanced MS lesions and how these lesions change over
      time; and (2) quantitative estimates of change in iron concentration by determining R2 (=
      1/T2) relaxation rate within MS lesions, normal appearing white matter, normal appearing gray
      matter, and other iron-rich regions within the brain before and after ferumoxytol injection.
    

Intervention name(s): Ferumoxytol
Intervention type(s): Drug
Intervention description(s): 510mg (17mL) IV
Intervention MeSH terms: Ferrosoferric Oxide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: MRI; Multiple Sclerosis; Healthy Volunteer