High-Field MRI Iron-Based Contrast-Enhanced Characterization of Multiple Sclerosis and Demyelinating Diseases

Sponsor

Stanford University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01973517

Collaborator

(none)

Enrollment

Locations

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Feraheme (ferumoxytol) is FDA-approved for iron supplementation and is composed of iron oxide nanoparticles classified among the ultra-small superparamagnetic iron oxides (USPIO). In this project we hypothesize that Feraheme could become a sensitive and specific marker of active inflammation in multiple sclerosis. We will explore this hypothesis taking advantage of ultra high field strength (7T) MRI to further increase the effectiveness of the contrast agent Feraheme at revealing inflammatory activity.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Feraheme Drug: Gadolinium-based contrast

Detailed Description

Multiple sclerosis (MS) is a neurological disorder that affects young adults world-wide. Feraheme (ferumoxytol) is FDA-approved for iron supplementation and is composed of iron oxide nanoparticles classified among the ultra-small superparamagnetic iron oxides (USPIO). After IV injection, the particles are taken up by the monocyte-macrophage system and can also be used to track macrophage infiltration by magnetic resonance imaging (MRI) after systemic injection owing to the strong image contrast of the iron-loaded macrophages. Approximately 24 hours after their IV injection, free particles are cleared from the circulation and MR signal alterations are thought to arise from the capture of particles by circulating phagocytic cells that are attracted to inflammatory lesions.

In this project we hypothesize that Feraheme could become a sensitive and specific marker of active inflammation in multiple sclerosis. We will explore this hypothesis by taking advantage of ultra high field strength (7T) MRI to further increase the effectiveness of the contrast agent Feraheme at revealing inflammatory activity.

Study Design

Study Type:

Observational

Actual Enrollment :

0 participants

Observational Model:

Case-Only

Time Perspective:

Cross-Sectional

Official Title:

7T MRI Ferumoxytol-Enhanced Characterization of Multiple Sclerosis and Demyelinating Diseases

Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Sep 1, 2018

Actual Study Completion Date :

Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Relapsing Remitting MS Patients with relapsing remitting multiple sclerosis will be imaged under high-field (7T) MRI prior to and following administration of gadolinium-based contrast (0.1 mmol/kg IV). Afterwards, they will be administered Feraheme 5mg/kg IV via slow push, and they will return 24 hours or later after pharmaceutical administration for post-Feraheme MR imaging.	Drug: Feraheme Patients with relapsing remitting multiple sclerosis will be administered Feraheme 5mg/kg IV via slow push once and imaged under high-field MRI at least 24 hours following administration, to allow for adequate clearance of intravascular pharmaceutical. Other Names: Ferumoxytol Drug: Gadolinium-based contrast Patients with relapsing remitting multiple sclerosis will be administered gadolinium-based contrast at a dose of 0.1 mmol/kg IV once and imaged under high-field MRI immediately following administration. Other Names: Gadolinium

Arm

Intervention/Treatment

Relapsing Remitting MS

Patients with relapsing remitting multiple sclerosis will be imaged under high-field (7T) MRI prior to and following administration of gadolinium-based contrast (0.1 mmol/kg IV). Afterwards, they will be administered Feraheme 5mg/kg IV via slow push, and they will return 24 hours or later after pharmaceutical administration for post-Feraheme MR imaging.

Drug: Feraheme

Patients with relapsing remitting multiple sclerosis will be administered Feraheme 5mg/kg IV via slow push once and imaged under high-field MRI at least 24 hours following administration, to allow for adequate clearance of intravascular pharmaceutical.

Other Names:

Ferumoxytol

Drug: Gadolinium-based contrast

Patients with relapsing remitting multiple sclerosis will be administered gadolinium-based contrast at a dose of 0.1 mmol/kg IV once and imaged under high-field MRI immediately following administration.

Other Names:

Gadolinium

Outcome Measures

Primary Outcome Measures

Number and location of enhancing brain lesions seen on 7 tesla MRI following Feraheme administration. [Baseline]
Magnetic resonance images of the brains of subjects will be evaluated independently by two expert readers blinded to the demographic and clinical data. The location and number of multiple sclerosis lesions that enhance following Feraheme administration will be recorded. These lesions will be compared with non-enhancing lesions and lesions that enhance with gadolinium-based contrast.

Secondary Outcome Measures

Number and location of enhancing brain lesions seen on 7 tesla MRI following gadolinium-based contrast administration. [Baseline]
Magnetic resonance images of the brains of subjects will be evaluated independently by two expert readers blinded to the demographic and clinical data. The location and number of multiple sclerosis lesions that enhance following gadolinium-based contrast administration will be recorded. These lesions will be compared with non-enhancing lesions and lesions that enhance with Ferahame.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients will be included if they are at least 18 years old and meet the revised diagnostic criteria for multiple sclerosis, relapsing remitting type.
Patients will be included based on MR evidence of disease activity after Gadolinium (enhanced lesion) on a previous screening MR in the previous 3 weeks days before Feraheme administration.

Exclusion Criteria:

Children (age < 18)
Those who lack decision-making capability
Contraindication to MRI such as pacemaker, other MR-incompatible metal implants or claustrophobia
Known allergy to dextran or drugs containing iron salts or any previous history of severe allergic reactions
Evidence of iron overload such as hemochromatosis or other hematologic disorders that imply iron level superior to the normal level.
Pregnancy or breast feeding.
History of renal disease or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) <40ml/min/1.73m?

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Richard M. Lucas Center for Imaging (of Stanford University)	Stanford	California	United States	94304
2	Stanford Hospitals and Clinics	Stanford	California	United States	94305