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

Primary Purpose

Multiple Sclerosis

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ferumoxytol

About this trial

This is an interventional diagnostic trial for Multiple Sclerosis focused on measuring MRI, Multiple Sclerosis, Healthy Volunteer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ferumoxytol

Arm Description

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

Outcomes

Primary Outcome Measures

change in gradient-echo T2*-weighted signal in an iron-rich brain structure, the globus pallidus

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02511028

First Posted

July 28, 2015

Last Updated

October 18, 2023

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborators

National Institutes of Health Clinical Center (CC)

1. Study Identification

Unique Protocol Identification Number

NCT02511028

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 29, 2023

Overall Recruitment Status

Completed

Study Start Date

November 27, 2015 (Actual)

Primary Completion Date

August 1, 2018 (Actual)

Study Completion Date

January 29, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborators

National Institutes of Health Clinical Center (CC)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

MRI, Multiple Sclerosis, Healthy Volunteer

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ferumoxytol

Arm Type

Experimental

Arm Description

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 Type

Drug

Intervention Name(s)

Ferumoxytol

Intervention Description

510mg (17mL) IV

Primary Outcome Measure Information:

Title

change in gradient-echo T2*-weighted signal in an iron-rich brain structure, the globus pallidus

Description

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

Time Frame

6 months following ferumoxytol administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel S Reich, M.D.

Organizational Affiliation

National Institute of Neurological Disorders and Stroke (NINDS)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2015-N-0156.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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