Clinical trial NCT04496830: SPINCOMS Biomarker Study
Official title: Cerebrospinal Fluid-biomarkers-based Diagnostic and Prognostic Models for Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: University of Colorado, Denver
name: University of Ottawa
name: Montana State University
First posted: 2020-08-03
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. 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.
2. 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).
3. 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.
4. To evaluate the MS severity score, the investigators will select 50 RRMS and 50 progressive MS (25 PPMS and 25 SPMS).
Primary purpose: DIAGNOSTIC

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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Biomarker Predicted Outcomes against NeurEx-based outcomes
timeFrame: 3 years
measure: MS Severity Model Analyses
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
Study officials:
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