Longitudinal Assessment of Iron Rims in MS Lesions

NCT05123443 | Recruiting DMC

• 1 other identifier: 21NS037
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

In multiple sclerosis (MS), the presence of white matter lesions surrounded by a rim of iron is suggested to signify a more severe disease course. Iron rim lesions can be detected through their appearance on susceptibility-based brain MRI at either 3-Tesla or 7-Tesla strength. We know that the formation of chronic active lesions is not uniform across MS cohorts so identifying risk factors which predispose individuals to the formation of rim lesions may provide a useful biomarker for clinical progression. One candidate set of risk factors include genetic variants which prevent some MS patients from resolving acute inflammation following their initial wave of inflammatory demyelination at lesion onset. Additionally, only small longitudinal clinical cohorts have reported the evolution of iron rim lesions many years after their initial formation, as well as their link to clinical disability or disease progression. NUH hold 7T-MRI scans of over 100 patients who received a research MRI with iron-sensitive sequences between 2008-2012. We will recruit 100 patients that received brain MRI several years ago to provide blood samples. The blood samples along with the previously acquired MRI scan will be sent to Johns Hopkins University in the US where genotyping studies will be performed to explore whether this genetic variation contributes to the accrual of chronic active rim lesions in MS. Patients who consent to provide blood samples will also have the option to consent to receive an additional 7-Tesla MRI scan which will allow us to compare how rim lesions evolve and whether their presence is correlated with disability. 30 MRI scans will initially be performed as funding for this amount is already secured. Following analysis of the pilot phase 1 data and securing additional funds, we will contact more patients who have already consented to receive the additional MRI to receive the scan

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• Cross-sectional: To identify gene variants or genetic network predictors of chronic perilesional inflammation in patients classified by the presence of rim lesions on brain MRI.

  Primary analyses will evaluate the pre-specified set of known MS-risk variants (both major histocompatibility \[MH\] and non-MH variants) as they relate to rim-lesion formation risk. Secondary unbiased analyses will evaluate novel variants contributing to rim lesion risk.

  12 months

• Longitudinal: To assess whether the presence and frequency of iron rim lesions in MS patients is associated with a more severe disability or disease course by comparing clinical and cognitive outcomes.

  Comparing changes between baseline and current iron rim lesion presence and count with the changes in clinical disability assessed with EDSS and ARMSS.

  9 months

Secondary Outcomes (2)

• Cross-sectional: To integrate genetic risk variant information.

  12 months

• Longitudinal: To assess long-term evolution of iron rim presence and frequency from T2* MRI scans of MS patients.

  9 months

Study Arms (2)

1 - Cross sectional genetics study

International, multicentre study assessing genetic predictors of chronic inflammation in 1000 MS patients with both susceptibility-based brain MRI scan and DNA from peripheral blood samples.The cross-sectional group will include 100 NUH participants who were previously scanned with iron sensitive sequences. These patients will be contacted by their clinical team and invited to participate. Blood samples will be stored in a -80° freezer until all 100 samples have been acquired. At this point, the samples will be shipped to the US for analysis, along with previously acquired MRI scans.

Biological: Blood sample provided

2 - Longitudinal cohort MRI study

The repeat MRI cohort group will be split into two phases. Phase 1: 30 participants who have consented to provide blood samples in the cross sectional genetics study will also be invited to participate by having an additional 7T MRI (funding already secured). Phase 2: Following completion of phase 1 and securing additional funds we aim to perform more scans to complete our analysis. Exact number of phase 2 participants will be determined from analysis of pilot data.

Diagnostic Test: 7-T MRI scan

Interventions

Blood sample provided BIOLOGICAL

Individuals who consent to provide a blood sample will be included in the cross-sectional genetics study.

1 - Cross sectional genetics study

7-T MRI scan DIAGNOSTIC_TEST

Individuals who consent to receive an additional 7-T MRI scan will be invited to the Sir Peter Mansfield Imaging Centre. This current MRI will be compared against the baseline 7-T scan performed between 2008 - 2012.

2 - Longitudinal cohort MRI study

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified through the clinical cohort that previously consented to research participation between 2008 - 2012 where susceptibility based brain MRI scans were obtained. From those who meet the above criteria, 100 participants will provide blood samples, 30 of those participants who consented to also receive an MRI will be invited to have a 7T MRI scan for phase 1 of the longitudinal study, and more participants will be recruited to phase 2 after the analysis of the pilot data.

You may qualify if:

• Men and women aged above 16 years
• Clinical diagnosis of MS as per revised McDonald Criteria 2017
• Existing susceptibility-weighted brain MRI scan
• Able to provide blood samples

You may not qualify if:

• Unwilling or unable to comply with the requirements of this protocol including the presence of any condition (physical, mental or social) that, in the opinion of the PI, is likely to affect the participants ability to comply with the study protocol.
• Unable to provide informed consent.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Nottingham University NHS Trust

Nottingham, United Kingdom

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Ryan Mamun

CONTACT

+447490225520; Ryan.Mamun1@nhs.net

Rasha Abdelfahim

CONTACT

rasha.abdelfahim@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2021
• First Posted: November 17, 2021
• Study Start: September 3, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

GB (1)