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

• ClinicalTrials.gov Identifier: NCT02511028
• Recruitment Status: Completed
• First Posted: July 29, 2015
• Last Update Posted: January 26, 2023
• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Collaborator: National Institutes of Health Clinical Center (CC)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information

• First Submitted Date: July 28, 2015
• First Posted Date: July 29, 2015
• Last Update Posted Date: January 26, 2023
• Actual Study Start Date: November 27, 2015
• Actual Primary Completion Date: August 1, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2022)

change in gradient-echo T2*-weighted signal in an iron-rich brain structure, the globus pallidus [ Time Frame: 6 months following ferumoxytol administration ]

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

• Original Primary Outcome Measures (submitted: July 28, 2015): Change in gradient-echo T2*-weighted signal in an iron-rich brain structure, the globus pallidus [ Time Frame: 6 months post tx ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Multiple Sclerosis

Intervention

Drug: Ferumoxytol

510mg (17mL) IV

Study Arms

Experimental: ferumoxytol

A 510 mg dose (17 mL) of ferumoxytol diluted in 50 mL of 0.9% normal saline will be intravenously infused over 17 minutes

Intervention: Drug: Ferumoxytol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 21, 2019): 14
• Original Estimated Enrollment (submitted: July 28, 2015): 20
• Actual Study Completion Date: January 29, 2019
• Actual Primary Completion Date: August 1, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02511028
• Other Study ID Numbers: 150156; 15-N-0156
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
• Original Responsible Party: National Institutes of Health Clinical Center (CC)
• Current Study Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Original Study Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Institutes of Health Clinical Center (CC)

Investigators

• Principal Investigator: Daniel S Reich, M.D.; National Institute of Neurological Disorders and Stroke (NINDS)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: January 20, 2023