SPINCOMS Biomarker Study

NCT04496830 | Completed

• 1 other identifier: 202004205
• Study Type: observational
• Target: 161
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (4)

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

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

Non-Inflammatory Neurological Diseases

* Clinical data questionnaire * CSF Analysis

Other Non-Inflammatory Neurological Diseases

* Clinical data questionnaire * CSF Analysis

Eligibility Criteria

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

Study Population

Relapsing-remitting multiple sclerosis patients Progressive multiple sclerosis patients Patients with non-inflammatory neurological diseases (NIND): e.g., ischemic-gliotic changes, CADASIL and other leukodystrophies, migraines, ischemic spinal cord lesions. Patients with other inflammatory neurological diseases (OIND):e.g. CNS Sjogren's, SLE, vasculitis, CNS infections, MOG-associated disorders, NMO spectrum disorders (NMOSD)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (1)

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (36)

• Kidd DP. Sarcoidosis of the central nervous system: clinical features, imaging, and CSF results. J Neurol. 2018 Aug;265(8):1906-1915. doi: 10.1007/s00415-018-8928-2. Epub 2018 Jun 19.

  PMID: 29922952 BACKGROUND

• Barbour C, Kosa P, Komori M, Tanigawa M, Masvekar R, Wu T, Johnson K, Douvaras P, Fossati V, Herbst R, Wang Y, Tan K, Greenwood M, Bielekova B. Molecular-based diagnosis of multiple sclerosis and its progressive stage. Ann Neurol. 2017 Nov;82(5):795-812. doi: 10.1002/ana.25083.

  PMID: 29059494 BACKGROUND

• Weideman AM, Tapia-Maltos MA, Johnson K, Greenwood M, Bielekova B. Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments. Front Neurol. 2017 Nov 10;8:577. doi: 10.3389/fneur.2017.00577. eCollection 2017.

  PMID: 29176956 BACKGROUND

• Kosa P, Komori M, Waters R, Wu T, Cortese I, Ohayon J, Fenton K, Cherup J, Gedeon T, Bielekova B. Novel composite MRI scale correlates highly with disability in multiple sclerosis patients. Mult Scler Relat Disord. 2015 Nov;4(6):526-35. doi: 10.1016/j.msard.2015.08.009. Epub 2015 Aug 28.

  PMID: 26590659 BACKGROUND

• Koga S, Aoki N, Uitti RJ, van Gerpen JA, Cheshire WP, Josephs KA, Wszolek ZK, Langston JW, Dickson DW. When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology. 2015 Aug 4;85(5):404-12. doi: 10.1212/WNL.0000000000001807. Epub 2015 Jul 2.

  PMID: 26138942 BACKGROUND

• Filippi M, Preziosa P, Meani A, Ciccarelli O, Mesaros S, Rovira A, Frederiksen J, Enzinger C, Barkhof F, Gasperini C, Brownlee W, Drulovic J, Montalban X, Cramer SP, Pichler A, Hagens M, Ruggieri S, Martinelli V, Miszkiel K, Tintore M, Comi G, Dekker I, Uitdehaag B, Dujmovic-Basuroski I, Rocca MA. Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study. Lancet Neurol. 2018 Feb;17(2):133-142. doi: 10.1016/S1474-4422(17)30469-6. Epub 2017 Dec 21.

  PMID: 29275979 BACKGROUND

• Kosa P, Barbour C, Wichman A, Sandford M, Greenwood M, Bielekova B. NeurEx: digitalized neurological examination offers a novel high-resolution disability scale. Ann Clin Transl Neurol. 2018 Sep 24;5(10):1241-1249. doi: 10.1002/acn3.640. eCollection 2018 Oct.

  PMID: 30349859 BACKGROUND

• Weideman AM, Barbour C, Tapia-Maltos MA, Tran T, Jackson K, Kosa P, Komori M, Wichman A, Johnson K, Greenwood M, Bielekova B. New Multiple Sclerosis Disease Severity Scale Predicts Future Accumulation of Disability. Front Neurol. 2017 Nov 10;8:598. doi: 10.3389/fneur.2017.00598. eCollection 2017.

  PMID: 29176958 BACKGROUND

• Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009 Oct;66(4):460-71. doi: 10.1002/ana.21867.

  PMID: 19847908 BACKGROUND

• Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.

  PMID: 28002688 BACKGROUND

• Kosa P, Ghazali D, Tanigawa M, Barbour C, Cortese I, Kelley W, Snyder B, Ohayon J, Fenton K, Lehky T, Wu T, Greenwood M, Nair G, Bielekova B. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment. Front Neurol. 2016 Aug 15;7:131. doi: 10.3389/fneur.2016.00131. eCollection 2016.

  PMID: 27574516 BACKGROUND

• Chen R, Mias GI, Li-Pook-Than J, Jiang L, Lam HY, Chen R, Miriami E, Karczewski KJ, Hariharan M, Dewey FE, Cheng Y, Clark MJ, Im H, Habegger L, Balasubramanian S, O'Huallachain M, Dudley JT, Hillenmeyer S, Haraksingh R, Sharon D, Euskirchen G, Lacroute P, Bettinger K, Boyle AP, Kasowski M, Grubert F, Seki S, Garcia M, Whirl-Carrillo M, Gallardo M, Blasco MA, Greenberg PL, Snyder P, Klein TE, Altman RB, Butte AJ, Ashley EA, Gerstein M, Nadeau KC, Tang H, Snyder M. Personal omics profiling reveals dynamic molecular and medical phenotypes. Cell. 2012 Mar 16;148(6):1293-307. doi: 10.1016/j.cell.2012.02.009.

  PMID: 22424236 BACKGROUND

• Bridel C, Eijlers AJC, van Wieringen WN, Koel-Simmelink M, Leurs CE, Schoonheim MM, Killestein J, Teunissen CE. No Plasmatic Proteomic Signature at Clinical Disease Onset Associated With 11 Year Clinical, Cognitive and MRI Outcomes in Relapsing-Remitting Multiple Sclerosis Patients. Front Mol Neurosci. 2018 Oct 31;11:371. doi: 10.3389/fnmol.2018.00371. eCollection 2018.

  PMID: 30429773 BACKGROUND

• Bergman J, Dring A, Zetterberg H, Blennow K, Norgren N, Gilthorpe J, Bergenheim T, Svenningsson A. Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm. 2016 Aug 2;3(5):e271. doi: 10.1212/NXI.0000000000000271. eCollection 2016 Oct.

  PMID: 27536708 BACKGROUND

• Kuhle J, Barro C, Disanto G, Mathias A, Soneson C, Bonnier G, Yaldizli O, Regeniter A, Derfuss T, Canales M, Schluep M, Du Pasquier R, Krueger G, Granziera C. Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Mult Scler. 2016 Oct;22(12):1550-1559. doi: 10.1177/1352458515623365. Epub 2016 Jan 11.

  PMID: 26754800 BACKGROUND

• Komori M, Blake A, Greenwood M, Lin YC, Kosa P, Ghazali D, Winokur P, Natrajan M, Wuest SC, Romm E, Panackal AA, Williamson PR, Wu T, Bielekova B. Cerebrospinal fluid markers reveal intrathecal inflammation in progressive multiple sclerosis. Ann Neurol. 2015 Jul;78(1):3-20. doi: 10.1002/ana.24408. Epub 2015 Apr 16.

  PMID: 25808056 BACKGROUND

• Komori M, Lin YC, Cortese I, Blake A, Ohayon J, Cherup J, Maric D, Kosa P, Wu T, Bielekova B. Insufficient disease inhibition by intrathecal rituximab in progressive multiple sclerosis. Ann Clin Transl Neurol. 2016 Feb 1;3(3):166-79. doi: 10.1002/acn3.293. eCollection 2016 Mar.

  PMID: 27042677 BACKGROUND

• Komori M, Kosa P, Stein J, Zhao V, Blake A, Cherup J, Sheridan J, Wu T, Bielekova B. Pharmacodynamic effects of daclizumab in the intrathecal compartment. Ann Clin Transl Neurol. 2017 May 29;4(7):478-490. doi: 10.1002/acn3.427. eCollection 2017 Jul.

  PMID: 28695148 BACKGROUND

• Gold L, Walker JJ, Wilcox SK, Williams S. Advances in human proteomics at high scale with the SOMAscan proteomics platform. N Biotechnol. 2012 Jun 15;29(5):543-9. doi: 10.1016/j.nbt.2011.11.016. Epub 2011 Dec 7.

  PMID: 22155539 BACKGROUND

• Masvekar R, Wu T, Kosa P, Barbour C, Fossati V, Bielekova B. Cerebrospinal fluid biomarkers link toxic astrogliosis and microglial activation to multiple sclerosis severity. Mult Scler Relat Disord. 2019 Feb;28:34-43. doi: 10.1016/j.msard.2018.11.032. Epub 2018 Dec 5.

  PMID: 30553167 BACKGROUND

• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.

  PMID: 6685237 BACKGROUND

• Roxburgh RH, Seaman SR, Masterman T, Hensiek AE, Sawcer SJ, Vukusic S, Achiti I, Confavreux C, Coustans M, le Page E, Edan G, McDonnell GV, Hawkins S, Trojano M, Liguori M, Cocco E, Marrosu MG, Tesser F, Leone MA, Weber A, Zipp F, Miterski B, Epplen JT, Oturai A, Sorensen PS, Celius EG, Lara NT, Montalban X, Villoslada P, Silva AM, Marta M, Leite I, Dubois B, Rubio J, Butzkueven H, Kilpatrick T, Mycko MP, Selmaj KW, Rio ME, Sa M, Salemi G, Savettieri G, Hillert J, Compston DA. Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity. Neurology. 2005 Apr 12;64(7):1144-51. doi: 10.1212/01.WNL.0000156155.19270.F8.

  PMID: 15824338 BACKGROUND

• Spitzer C, Bouchain M, Winkler LY, Wingenfeld K, Gold SM, Grabe HJ, Barnow S, Otte C, Heesen C. Childhood trauma in multiple sclerosis: a case-control study. Psychosom Med. 2012 Apr;74(3):312-8. doi: 10.1097/PSY.0b013e31824c2013. Epub 2012 Mar 9.

  PMID: 22408134 BACKGROUND

• gbm: Generalized Boosted Regression Models [computer program]. Version 2.1 2013.

  BACKGROUND

• Sipe JC, Knobler RL, Braheny SL, Rice GP, Panitch HS, Oldstone MB. A neurologic rating scale (NRS) for use in multiple sclerosis. Neurology. 1984 Oct;34(10):1368-72. doi: 10.1212/wnl.34.10.1368.

  PMID: 6541311 BACKGROUND

• Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, Mills JA, Weiner HL. Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 1983 Jan 27;308(4):173-80. doi: 10.1056/NEJM198301273080401.

  PMID: 6294517 BACKGROUND

• Schmidt F, Oliveira AL, Araujo A. Development and Validation of a Neurological Disability Scale for Patients with HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP): The IPEC-1 Scale. Neurology 2012;78.

  BACKGROUND

• Fischer JS, Rudick RA, Cutter GR, Reingold SC. The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler. 1999 Aug;5(4):244-50. doi: 10.1177/135245859900500409.

  PMID: 10467383 BACKGROUND

• Sun YV. Multigenic modeling of complex disease by random forests. Adv Genet. 2010;72:73-99. doi: 10.1016/B978-0-12-380862-2.00004-7.

  PMID: 21029849 BACKGROUND

• Sun BB, Maranville JC, Peters JE, Stacey D, Staley JR, Blackshaw J, Burgess S, Jiang T, Paige E, Surendran P, Oliver-Williams C, Kamat MA, Prins BP, Wilcox SK, Zimmerman ES, Chi A, Bansal N, Spain SL, Wood AM, Morrell NW, Bradley JR, Janjic N, Roberts DJ, Ouwehand WH, Todd JA, Soranzo N, Suhre K, Paul DS, Fox CS, Plenge RM, Danesh J, Runz H, Butterworth AS. Genomic atlas of the human plasma proteome. Nature. 2018 Jun;558(7708):73-79. doi: 10.1038/s41586-018-0175-2. Epub 2018 Jun 6.

  PMID: 29875488 BACKGROUND

• Calle ML, Urrea V, Boulesteix AL, Malats N. AUC-RF: a new strategy for genomic profiling with random forest. Hum Hered. 2011;72(2):121-32. doi: 10.1159/000330778. Epub 2011 Oct 11.

  PMID: 21996641 BACKGROUND

• Friedman J.Greedy function approximation: the gradient boosting machine. Annals of Statistics 2001;29:1189-1232.

  BACKGROUND

• Sheridan LK, Fitzgerald HE, Adams KM, Nigg JT, Martel MM, Puttler LI, Wong MM, Zucker RA. Normative Symbol Digit Modalities Test performance in a community-based sample. Arch Clin Neuropsychol. 2006 Jan;21(1):23-8. doi: 10.1016/j.acn.2005.07.003. Epub 2005 Aug 31.

  PMID: 16139470 BACKGROUND

• Learmonth YC, Motl RW, Sandroff BM, Pula JH, Cadavid D. Validation of patient determined disease steps (PDDS) scale scores in persons with multiple sclerosis. BMC Neurol. 2013 Apr 25;13:37. doi: 10.1186/1471-2377-13-37.

  PMID: 23617555 BACKGROUND

• Kragt JJ, Thompson AJ, Montalban X, Tintore M, Rio J, Polman CH, Uitdehaag BM. Responsiveness and predictive value of EDSS and MSFC in primary progressive MS. Neurology. 2008 Mar 25;70(13 Pt 2):1084-91. doi: 10.1212/01.wnl.0000288179.86056.e1. Epub 2008 Jan 9.

  PMID: 18184917 BACKGROUND

• Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB, Ferrante RJ, Fillit H, Finkelstein R, Fisher M, Gendelman HE, Golub RM, Goudreau JL, Gross RA, Gubitz AK, Hesterlee SE, Howells DW, Huguenard J, Kelner K, Koroshetz W, Krainc D, Lazic SE, Levine MS, Macleod MR, McCall JM, Moxley RT 3rd, Narasimhan K, Noble LJ, Perrin S, Porter JD, Steward O, Unger E, Utz U, Silberberg SD. A call for transparent reporting to optimize the predictive value of preclinical research. Nature. 2012 Oct 11;490(7419):187-91. doi: 10.1038/nature11556.

  PMID: 23060188 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Cerebrospinal fluids

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

Study Design

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

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: August 3, 2020
• Study Start: June 15, 2020
• Primary Completion: November 24, 2023
• Study Completion: November 24, 2023
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

US (1)