SPINCOMS Biomarker Study

Multiple Sclerosis Clinical Trial

— SPINCOMS  

Official title:

Cerebrospinal Fluid-biomarkers-based Diagnostic and Prognostic Models for Multiple Sclerosis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04496830
• Other study ID #: 202004205
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 15, 2020
• Est. completion date: March 1, 2024

Study information

• Verified date: April 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine if biomarker-based CSF testing is reliably detecting differences between patients with Multiple Sclerosis (MS), different MS-subtypes, and other central nervous system (CNS) diseases. This study will also look to identify biomarkers that could be used for the prediction, at the time of diagnosis, of the future disease clinical course and response to therapy. The SOMAscan assay will be used for CSF samples analysis.

Description:

Using machine learning, the investigators have developed from SOMAScan: 1. A molecular diagnostic test that differentiates MS from other inflammatory and non-inflammatory central nervous system (CNS) diseases (area under receiver-operator characteristic curve-AUROC of 0.98); 2. A molecular test that differentiates relapsing-remitting MS from progressive MS variants (AUROC of 0.91); and 3. A molecular test that predicts future rates of disability progression, concordance coefficient of 0.425 (p<0.001). Because these results are derived from a single research center (NIAID/NDS), it is imperative to determine their performance in real clinical practice settings as a necessary step for their potential regulatory approval. Consequently, this application has 2 specific aims: AIM 1. To independently validate afore-mentioned CSF-biomarker-based tests for their clinical value within the multicenter Spinal fluid Consortium for MS (SPINCOMS). In Aim 1, each of the 3 defined tests will be validated in 100 new SPINCOMS patients. To validate the prognostic test, 100 MS patients with CSF collected at least 3 years ago will be evaluated at follow-up examination with standardized clinical outcomes. CSF will be analyzed blinded using pre-defined statistical models. AIM 2. To explore whether collected CSF-biomarkers point towards pathogenic heterogeneity that may predict patient-specific efficacy for different disease-modifying treatments (DMTs) or identify pathogenic mechanisms not targeted by current DMTs. In Aim 2, clustering analysis will assess pathogenic heterogeneity and explore potential predictors of response to therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: March 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

MS Patients selection criteria

• Lumbar puncture (LP) in the untreated stage with cryopreserved CSF (serum/blood optional) with consent to use it for future research
• = 3 and = 10 years of follow-up from LP
• At time of LP untreated and not treated with steroid or off steroids = one month
• Available/willing to come for in-person follow-up
• Available/willing to sign the NIH 09-I-0032 "Sample processing only" consent form
• Diagnosis of MS based on 2017 McDonald criteria at time of follow-up visit Non-MS Patients selection criteria Required: 25 Non-Inflammatory Neurological Disease (NIND), 25 Other Inflammatory Neurological Disease (OIND)
• Lumbar puncture (LP) in the untreated stage with cryopreserved CSF (serum/blood optional) with consent to use it for future research
• = 3 and = 10 years of follow-up from LP
• At time of LP untreated and not treated with steroid or off steroids = one month
• Up to date contact information
• Available/willing to sign the NIH 09-I-0032 "Sample processing only" consent form
• Diagnosis:

NIND: e.g., ischemic-gliotic changes, CADASIL and other leukodystrophies, migraines, ischemic spinal cord lesions etc OIND: e.g. CNS Sjogren's, SLE, vasculitis, CNS infections, MOG-associated disorders, NMO spectrum disorders (NMOSD)

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Device:
• SOMAscan
Analysis of previously donated cerebrospinal fluid using a SOMAscan assay

Locations

Country	Name	City	State
United States	Washington University in St Louis	Saint Louis	Missouri

Sponsors (5)

Lead Sponsor	Collaborator
Washington University School of Medicine	Montana State University, National Institute of Allergy and Infectious Diseases (NIAID), University of Colorado, Denver, University of Ottawa

Country where clinical trial is conducted

United States, 

References & Publications (36)

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* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarker Predicted Outcomes against NeurEx-based outcomes	CSF-biomarker-predicted outcomes against measured NeurEx-based outcomes, considering a Bonferroni-adjusted significance level 0.05/3 = 0.017 (to adjust for 3 tests).	3 years
Primary	MS Severity Model Analyses	As secondary analyses of MS severity model,assessment of correlations between CSF-biomarker-predicted outcomes and more traditional MS outcomes. Specifically, correlate CSF-biomarker-based scores of MS severity and MSSS, ARMSSS and by MS-DSS, calculated from the follow-up visit scores. Based on power calculations, 100 relevant patients/classifier will provide > 90% power to externally validate all 3 Somascan CSF-biomarker-based models.	3 years