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

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ClinicalTrials.gov Identifier: NCT02511028
Recruitment Status : Completed
First Posted : July 29, 2015
Last Update Posted : January 26, 2023
Sponsor:
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  ICMJE July 28, 2015
First Posted Date  ICMJE July 29, 2015
Last Update Posted Date January 26, 2023
Actual Study Start Date  ICMJE November 27, 2015
Actual Primary Completion Date August 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE In Vivo Characterization of Inflammation With Ferumoxytol, an Ultrasmall Superparamagnetic Iron Oxide Nanoparticle, on 7 Tesla Magnetic Resonance Imaging
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Drug: Ferumoxytol
510mg (17mL) IV
Study Arms  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
14
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2015)
20
Actual Study Completion Date  ICMJE January 29, 2019
Actual Primary Completion Date August 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02511028
Other Study ID Numbers  ICMJE 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  ICMJE 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  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Original Study Sponsor  ICMJE National Institutes of Health Clinical Center (CC)
Collaborators  ICMJE National Institutes of Health Clinical Center (CC)
Investigators  ICMJE
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

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP