SPINCOMS Biomarker Study

Sponsor

Washington University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT04496830

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID) (NIH), University of Colorado, Denver (Other), University of Ottawa (Other), Montana State University (Other)

150

Enrollment

Location

Arms

36.5

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Device: SOMAscan	N/A

Detailed Description

Using machine learning, the investigators have developed from SOMAScan:

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);
A molecular test that differentiates relapsing-remitting MS from progressive MS variants (AUROC of 0.91); and
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

For the MS diagnostic test, the investigators will select 50 patients with definite MS (CIS/RIS excluded) and 50 controls, including 25 non-inflammatory neurological diseases (NIND) that mimic MS (such as patients with vascular-ischemic changes, complex migraines, leukodystrophies, etc.) and 25 other inflammatory neurological diseases (OIND) such as NMO, Susac's syndrome, sarcoidosis, CNS vasculitis. For validating the RRMS versus progressive MS classifier, the investigators will select CSF from 50 RRMS and 50 progressive MS patients (25 SPMS and 25 PPMS). Cryopreserved CSF samples from these patients will be analyzed blindly using SOMAscan assay. Probability of MS diagnosis and progressive MS diagnosis will be calculated based on published models. Results will then be unblinded and analyzed for accuracy of diagnostic conclusion. To evaluate the MS severity score, the investigators will select 50 RRMS and 50 progressive MS (25 PPMS and 25 SPMS).For the MS diagnostic test, the investigators will select 50 patients with definite MS (CIS/RIS excluded) and 50 controls, including 25 non-inflammatory neurological diseases (NIND) that mimic MS (such as patients with vascular-ischemic changes, complex migraines, leukodystrophies, etc.) and 25 other inflammatory neurological diseases (OIND) such as NMO, Susac's syndrome, sarcoidosis, CNS vasculitis. For validating the RRMS versus progressive MS classifier, the investigators will select CSF from 50 RRMS and 50 progressive MS patients (25 SPMS and 25 PPMS). Cryopreserved CSF samples from these patients will be analyzed blindly using SOMAscan assay. Probability of MS diagnosis and progressive MS diagnosis will be calculated based on published models. Results will then be unblinded and analyzed for accuracy of diagnostic conclusion. To evaluate the MS severity score, the investigators will select 50 RRMS and 50 progressive MS (25 PPMS and 25 SPMS).

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Jun 15, 2020

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relapsing Remitting Multiple Sclerosis Blood sample collection Vital signs, weight, height and BMI. Complete neurological examination documented in NeurEx (recorded with an iPAD). Clinical data questionnaire 25FW & non-dominant hand 9HPT (required for calculating CombiWISE & MS-DSS). Smartphone Apps (include 25FW, SDMT and tests that correlate highly w 9HPT - can be acquired in patient-autonomous manner with minimal assistance). Optical Coherence Tomography (OCT) CSF Analysis	Device: SOMAscan Analysis of previously donated cerebrospinal fluid using a SOMAscan assay
Experimental: Progressive Multiple Sclerosis Blood sample collection Vital signs, weight, height and BMI. Complete neurological examination documented in NeurEx (recorded with an iPAD). Clinical data questionnaire 25FW & non-dominant hand 9HPT (required for calculating CombiWISE & MS-DSS). Smartphone Apps (include 25FW, SDMT and tests that correlate highly w 9HPT - can be acquired in patient-autonomous manner with minimal assistance). Optical Coherence Tomography (OCT) CSF Analysis	Device: SOMAscan Analysis of previously donated cerebrospinal fluid using a SOMAscan assay
Experimental: Non-Inflammatory Neurological Diseases Clinical data questionnaire CSF Analysis	Device: SOMAscan Analysis of previously donated cerebrospinal fluid using a SOMAscan assay
Experimental: Other Non-Inflammatory Neurological Diseases Clinical data questionnaire CSF Analysis	Device: SOMAscan Analysis of previously donated cerebrospinal fluid using a SOMAscan assay

Outcome Measures

Primary Outcome Measures

Biomarker Predicted Outcomes against NeurEx-based outcomes [3 years]
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).
MS Severity Model Analyses [3 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University in St Louis	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Washington University School of Medicine

ClinicalTrials.gov Identifier:

NCT04496830

Other Study ID Numbers:

202004205

First Posted:

Aug 3, 2020

Last Update Posted:

Apr 26, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Multiple Sclerosis

Sclerosis

Study Results

No Results Posted as of Apr 26, 2022