Novel Imaging Markers in SPMS

Sponsor

University of Utah (Other)

Overall Status

Recruiting

CT.gov ID

NCT05357833

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot study takes the innovative approach of using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle enhanced MRI to measure activity of the innate immune system within MS lesions. Activity of innate immunity has been hypothesized as one of the critical pathologic processes underpinning neurologic worsening in progressive MS. As such, in the short term this project proposes to investigate USPIO uptake in SPMS lesions as a promising in vivo imaging biomarker for chronic-active lesions, as distinguished from chronic-inactive lesions.

Condition or Disease	Intervention/Treatment	Phase
Secondary Progressive Multiple Sclerosis Multiple Sclerosis, Secondary Progressive Multiple Sclerosis	Drug: Ferumoxytol infusion Drug: Gadoteridol Diagnostic Test: MRI Brain and Cervical Spine	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Novel Imaging Markers of Innate Immune Activation in Secondary Progressive Multiple Sclerosis

Actual Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

May 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SPMS Cohort Subjects will undergo MR imaging of the brain and cervical spine for pre- and post-administration of gadoteridol (0.2 mL/kg), then pre- and post-administration of ferumoxytol (4 mg/kg). Scans will be obtained over the course of two separate imaging visits.	Drug: Ferumoxytol infusion Subjects will receive a single, weighted dose of intravenous ferumoxytol (4 mg/kg) diluted in 50 mL of saline. Other Names: Feraheme Drug: Gadoteridol Subjects will receive a single, weighted dose of intravenous gadoteridol (0.2 mL/kg). Other Names: ProHance, gadolinium-based MRI contrast agent Diagnostic Test: MRI Brain and Cervical Spine 3T MR imaging of the brain and cervical spine pre- and post-administration of gadolinium, then pre- and 96 hours (±24 hours) post-administration of ferumoxytol

Arm

Intervention/Treatment

Experimental: SPMS Cohort

Subjects will undergo MR imaging of the brain and cervical spine for pre- and post-administration of gadoteridol (0.2 mL/kg), then pre- and post-administration of ferumoxytol (4 mg/kg). Scans will be obtained over the course of two separate imaging visits.

Drug: Ferumoxytol infusion

Subjects will receive a single, weighted dose of intravenous ferumoxytol (4 mg/kg) diluted in 50 mL of saline.

Other Names:

Feraheme

Drug: Gadoteridol

Subjects will receive a single, weighted dose of intravenous gadoteridol (0.2 mL/kg).

Other Names:

ProHance, gadolinium-based MRI contrast agent

Diagnostic Test: MRI Brain and Cervical Spine

3T MR imaging of the brain and cervical spine pre- and post-administration of gadolinium, then pre- and 96 hours (±24 hours) post-administration of ferumoxytol

Outcome Measures

Primary Outcome Measures

Signal change on T1-weighted and 3D UTE MRI brain (and upper cervical cord) before and 96 hours (±24 hours) after ferumoxytol administration [96 hours ±24 hours]

Secondary Outcome Measures

Incidence of treatment-emergent adverse events (safety and tolerability) [96 hours ±24 hours]
Assess the safety and tolerability of ferumoxytol in Secondary Progressive MS cohort based on Adverse Events

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults age 35 to 65 years
Clinically diagnosed with secondary progressive multiple sclerosis (SPMS) (2017 McDonald Criteria)
Worsening 25 foot walk time (worsening SPMS cohort) over the preceding 2 years.
Ambulatory with ability to walk at least 20 meters without rest, with or without aid
Ability and willingness to attend study visits and complete the study

Exclusion Criteria:

Clinically diagnosed with relapsing remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), clinical isolated syndrome (CIS), or radiologically isolated syndrome (RIS)
Clinical MS relapse and/or new MRI lesion(s) within the preceding 2 years
Positive pregnancy test
Gadolinium contrast allergy
Acute or chronic kidney disease with eGFR <30 ml/min/1.73m2
Pacemaker or other MRI contraindications per American College of Radiology guidelines
Intravenous iron sensitivity
Serum ferritin and transferrin saturation above age-adjusted upper limit of normal (if serum ferritin is above normal, but transferrin saturation is normal, the subject is NOT excluded)