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In Vivo Characterization of Inflammation With Ferumoxytol, an Ultrasmall Superparamagnetic Iron Oxide Nanoparticle, on 7 Tesla Magnetic Resonance Imaging

Phase 1
Completed
Conditions
Multiple Sclerosis
Interventions
Registration Number
NCT02511028
Lead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
14
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ferumoxytolFerumoxytolA 510 mg dose (17 mL) of ferumoxytol diluted in 50 mL of 0.9% normal saline will be intravenously infused over 17 minutes
Primary Outcome Measures
NameTimeMethod
change in gradient-echo T2*-weighted signal in an iron-rich brain structure, the globus pallidus6 months following ferumoxytol administration

determine if ferumoxytol induces long-lasting brain signal intensity changes in HV and MS

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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