Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06591429
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-07
Brief Title:
Smoldering Inflammation in MS
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Investigation of Smoldering Inflammation in Multiple Sclerosis
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this observational study is to learn about inflammation in those with relapsing remitting Multiple Sclerosis MS The main questions it aims to answer are
How does abnormal neural inflammation compare to cellular and molecular inflammation in MS
Once treated why does abnormal inflammation persist
How does abnormal neural inflammation compare to cellular and molecular inflammation in MS
Once treated why does abnormal inflammation persist
Detailed Description:
The purpose of this study is to combine multi-tracer PET and high-resolution CSF analysis to understand the inflammatory landscape of MS and to identify components of inflammation which do not resolve with high-efficacy DMT and are hypothesized to drive disability accumulation via smoldering inflammation Identification of components of the pathologic cascade which do not respond to extant therapies will motivate future complementary therapies targeted at yet untreated MS pathology
Current MS disease modifying therapies DMT focus on reducing the inflammatory or auto-immune component of the disease Highly effective DMTs are incredibly effective at reducing this inflammation such that new lesions and clinical relapses are increasingly rare However despite these advances most patients will experience clinical worsening independent of relapse activity This eventually manifests as progressive MS and stubbornly resists therapy One hypothesized driver of this clinical progression is smoldering inflammation Smoldering inflammation is defined as ongoing inflammation sufficient to cause accumulating tissue injury but insufficient to cause clinical relapse The nature of this smoldering inflammation is poorly understood Emerging imaging biomarkers have identified smoldering inflammation but those markers are not well-linked to cellular mechanisms A key innovation of this approach is that by comparing pre- vs post-treatment single-cell RNA sequencing data we will identify cell populations that are most sensitive and resistant to treatment and relate these findings to imaging changes Identifying components of persistent inflammation may identify future treatment targets
25 adult patients with relapsing remitting multiple sclerosis will be enrolled in this study Patients will be recruited from the John L Trotter MS Center at Washington University in St Louis Participants will be referred to the study by their treating neurologist
11C-CS1P1 and 11C-DPA-713 are the investigational radiotracers used in this study Participation in this study consists of several visits Visits include 1 pre-screening and clinical 2 baseline lumbar puncture 3 baseline 11C-DPA-713 PETCT 4 baseline 11C-CS1P1 PETCT 5 baseline 18F-FDG PETMRI 6 follow-up lumbar puncture 7 follow-up 11C-DPA-713 PETCT 8 follow-up 11C-CS1P1 PETCT and 9 follow-up 18F-FDG PETMRI Baseline and follow-up visits of the same type eg 3 and 7 are identical with baseline occurring at enrollment and follow-up occurring at least nine months but no more than 12 months after DMT initiation Screening session must precede the clinical sessions At each the baseline and follow-up time point the lumbar puncture and each imaging session may occur in any order At baseline and follow up all sessions will take place within approximately 1 month Multiple sessions can occur on the same day Consecutive imaging sessions will be separated by 6 half-lives of the initially injected radiotracer
This pilot study will link the molecular specificity and high spatial resolution of combined positron emission tomography and magnetic resonance imaging with the molecular explanatory power of single-cell RNA sequencing to investigate the effects of B cell depletion or other similarly efficacious treatments on smoldering inflammation and characterize the nature of persistent inflammation which contributes to disability in patients with MS A key innovation of this approach is that by comparing pre- vs post-treatment single-cell RNA sequencing data we will identify cell populations that are most sensitive and resistant to treatment and relate these findings to imaging changes Identifying components of persistent inflammation may identify future treatment targets
Current MS disease modifying therapies DMT focus on reducing the inflammatory or auto-immune component of the disease Highly effective DMTs are incredibly effective at reducing this inflammation such that new lesions and clinical relapses are increasingly rare However despite these advances most patients will experience clinical worsening independent of relapse activity This eventually manifests as progressive MS and stubbornly resists therapy One hypothesized driver of this clinical progression is smoldering inflammation Smoldering inflammation is defined as ongoing inflammation sufficient to cause accumulating tissue injury but insufficient to cause clinical relapse The nature of this smoldering inflammation is poorly understood Emerging imaging biomarkers have identified smoldering inflammation but those markers are not well-linked to cellular mechanisms A key innovation of this approach is that by comparing pre- vs post-treatment single-cell RNA sequencing data we will identify cell populations that are most sensitive and resistant to treatment and relate these findings to imaging changes Identifying components of persistent inflammation may identify future treatment targets
25 adult patients with relapsing remitting multiple sclerosis will be enrolled in this study Patients will be recruited from the John L Trotter MS Center at Washington University in St Louis Participants will be referred to the study by their treating neurologist
11C-CS1P1 and 11C-DPA-713 are the investigational radiotracers used in this study Participation in this study consists of several visits Visits include 1 pre-screening and clinical 2 baseline lumbar puncture 3 baseline 11C-DPA-713 PETCT 4 baseline 11C-CS1P1 PETCT 5 baseline 18F-FDG PETMRI 6 follow-up lumbar puncture 7 follow-up 11C-DPA-713 PETCT 8 follow-up 11C-CS1P1 PETCT and 9 follow-up 18F-FDG PETMRI Baseline and follow-up visits of the same type eg 3 and 7 are identical with baseline occurring at enrollment and follow-up occurring at least nine months but no more than 12 months after DMT initiation Screening session must precede the clinical sessions At each the baseline and follow-up time point the lumbar puncture and each imaging session may occur in any order At baseline and follow up all sessions will take place within approximately 1 month Multiple sessions can occur on the same day Consecutive imaging sessions will be separated by 6 half-lives of the initially injected radiotracer
This pilot study will link the molecular specificity and high spatial resolution of combined positron emission tomography and magnetic resonance imaging with the molecular explanatory power of single-cell RNA sequencing to investigate the effects of B cell depletion or other similarly efficacious treatments on smoldering inflammation and characterize the nature of persistent inflammation which contributes to disability in patients with MS A key innovation of this approach is that by comparing pre- vs post-treatment single-cell RNA sequencing data we will identify cell populations that are most sensitive and resistant to treatment and relate these findings to imaging changes Identifying components of persistent inflammation may identify future treatment targets
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None