Novel Imaging Markers in SPMS

NCT05357833 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 00147230
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Secondary Progressive Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis

Keywords

Perilesional microglia; Ferumoxytol; USPIO; Utrasmall superparamagnetic iron oxide nanoparticles; Infiltrating macrophages; Activated microglia; USPIO enhancement

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Incidence of treatment-emergent adverse events (safety and tolerability)

  96 hours ±24 hours

Study Arms (1)

SPMS Cohort

EXPERIMENTAL

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; Drug: Gadoteridol; Diagnostic Test: MRI Brain and Cervical Spine

Interventions

Ferumoxytol infusion DRUG

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

Also known as: Feraheme

SPMS Cohort

Gadoteridol DRUG

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

Also known as: ProHance, gadolinium-based MRI contrast agent

SPMS Cohort

MRI Brain and Cervical Spine DIAGNOSTIC_TEST

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

SPMS Cohort

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah Health Imaging and Neurosciences Center

Salt Lake City, Utah, 84108, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

Ferrosoferric Oxide; gadoteridol

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals

Study Officials

• M. Mateo Paz Soldan, MD, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Neurology, Division of Neuroimmunology

Study Record Dates

• First Submitted: April 25, 2022
• First Posted: May 3, 2022
• Study Start: June 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)