Novel Imaging Markers in SPMS

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive; Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Ferumoxytol infusion; Drug: Gadoteridol; Diagnostic test: MRI Brain and Cervical Spine

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health Imaging and Neurosciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: M. Mateo Paz Soldan, MD, PhD, University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: April 25, 2022
• First Submitted That Met QC Criteria: May 1, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Ferumoxytol; USPIO; Perilesional microglia; Utrasmall superparamagnetic iron oxide nanoparticles; Infiltrating macrophages; Activated microglia; USPIO enhancement
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Neoplastic Processes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Neoplasm Metastasis; Hematinics; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: 00147230

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No