In Vivo Characterization of Inflammation With Ferumoxytol, an Ultrasmall Superparamagnetic Iron Oxide Nanoparticle, on 7 Tesla Magnetic Resonance Imaging
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Multiple Sclerosis |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 18 - 70 |
| Updated: | 3/24/2019 |
| Start Date: | July 28, 2015 |
| End Date: | January 29, 2019 |
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.
- 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.
- 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.
- 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.
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.
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.
- INCLUSION CRITERIA:
HEALTHY VOLUNTEER INCLUSION CRITERIA
- age between 18 and 70 (inclusive)
- able to give informed consent
- brain MRI within 2 years of study enrollment that shows no clinically significant
abnormalities, in the judgment of a board-certified and NIH-credentialed
neuroradiologist
PATIENT INCLUSION CRITERIA
- age between 18 and 70, inclusive
- able to give informed consent
- diagnosis of multiple sclerosis according to revised McDonald Criteria
EXCLUSION CRITERIA:
GENERAL EXCLUSION CRITERIA:
- screening labs demonstrating any value for hepatic or renal function levels out of the
range of normal, to include AST, ALT, bilirubin, alkaline phosphatase, creatinine,
eGFR
- evidence of polycythemia vera with hemoglobin levels more than 1 standard deviation
above the NIH laboratory s normal level
- iron overload syndromes, including hemochromatosis, or subjects with evidence of iron
overload with a baseline ferritin level greater than 370 ng/ml and percent saturation
of transferrin level greater than 40%.
- previous or current alcohol and/or substance abuse per medical history or medical
records
- medical contraindications for MRI (e.g., any non-organic implant or other device such
as a cardiac pacemaker or infusion pump or other metallic implants, objects, or body
piercings that are not MRI-compatible or cannot be removed)
- psychological contraindications for MRI (e.g., claustrophobia), to be assessed at the
time the medical history is collected
- pregnancy or current breastfeeding
- reported history of clinically significant impaired hearing, because people with
impaired hearing are at increased risk of sound-induced damage from the MRI scanner
- known allergy to dextran or drugs containing iron salts or any previous history of
severe allergic reactions, anaphylaxis, to any drug
- clinically significant medical or neurological disorders that, in the judgment of the
investigators might expose the patient to undue risk of harm confound study outcomes
or prevent the participant from completing the study; examples of such conditions
include but are not limited to diagnosis of certain types of cancer, cardiopulmonary
conditions such as congestive heart failure, or uncontrolled hypertension
ADDITIONAL PATIENT EXCLUSION CRITERION:
-4 or more gadolinium-enhancing lesions on the screening scan
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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