Novel Imaging Markers in SPMS

Study Overview
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Brief Summary
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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.

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

Conditions
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Secondary Progressive Multiple Sclerosis, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis

Intervention / Treatment
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* Drug: Ferumoxytol infusion
* Drug: Gadoteridol
* Diagnostic Test: MRI Brain and Cervical Spine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPMS Cohort<br>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<br>* Subjects will receive a single, weighted dose of intravenous ferumoxytol (4 mg/kg) diluted in 50 mL of saline.<br>* Other names: Feraheme;Drug: Gadoteridol<br>* Subjects will receive a single, weighted dose of intravenous gadoteridol (0.2 mL/kg).<br>* Other names: ProHance, gadolinium-based MRI contrast agent;Diagnostic Test: MRI Brain and Cervical Spine<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (safety and tolerability) | Assess the safety and tolerability of ferumoxytol in Secondary Progressive MS cohort based on Adverse Events | 96 hours ±24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Perilesional microglia, Ferumoxytol, USPIO, Utrasmall superparamagnetic iron oxide nanoparticles, Infiltrating macrophages, Activated microglia, USPIO enhancement