Secondary Progressive Multiple Sclerosis, Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis
Conditions
Keywords
Perilesional microglia, Ferumoxytol, USPIO, Utrasmall superparamagnetic iron oxide nanoparticles, Infiltrating macrophages, Activated microglia, USPIO enhancement
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.
Interventions
Subjects will receive a single, weighted dose of intravenous ferumoxytol (4 mg/kg) diluted in 50 mL of saline.
DRUGGadoteridol
Subjects will receive a single, weighted dose of intravenous gadoteridol (0.2 mL/kg).
DIAGNOSTIC_TESTMRI 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
Sponsors
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Adults age 35 to 65 years 2. Clinically diagnosed with secondary progressive multiple sclerosis (SPMS) (2017 McDonald Criteria) 3. Worsening 25 foot walk time (worsening SPMS cohort) over the preceding 2 years. 4. Ambulatory with ability to walk at least 20 meters without rest, with or without aid 5. Ability and willingness to attend study visits and complete the study
Exclusion criteria
1. Clinically diagnosed with relapsing remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS), clinical isolated syndrome (CIS), or radiologically isolated syndrome (RIS) 2. Clinical MS relapse and/or new MRI lesion(s) within the preceding 2 years 3. Positive pregnancy test 4. Gadolinium contrast allergy 5. Acute or chronic kidney disease with eGFR \<30 ml/min/1.73m2 6. Pacemaker or other MRI contraindications per American College of Radiology guidelines 7. Intravenous iron sensitivity 8. 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)
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed