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Multicenter Study
. 2024 Jul 2:15:1380025.
doi: 10.3389/fimmu.2024.1380025. eCollection 2024.

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT)

Sara Samadzadeh  1   2   3 , Rafl Adnan  1   2 , Paulina Berglova  2 , Mahdi Barzegar  4 , Birgit Debrabant  5 , Stine Gundtoft Roikjaer  1   2   6 , Michael Levy  7 , Axel Petzold  8   9   10 , Jacqueline Palace  11 , Eoin P Flanagan  12 , Sara Mariotto  13 , Soeren T Skou  6   14 , Anne Froelich  2   15   16 , Itay Lotan  17   18 , Silvia Messina  11 , Ruth Geraldes  11 , Susanna Asseyer  3   19   20   21 , Hadas Stiebel-Kalish  18   22   23 , Frederike Cosima Oertel  3   19   20   21 , Vahid Shaygannejad  4 , Mohammad Ali Sahraian  24 , Ho Jin Kim  25 , Jeffrey L Bennett  26 , Chotima Böttcher  3   19   20 , Hanna G Zimmermann  3   19   20   21   27 , Brian G Weinshenker  28 , Friedemann Paul  3   19   20   21 , Nasrin Asgari  1   2   29
Affiliations
Multicenter Study

Protocol of a prospective multicenter study on comorbidity impact on multiple sclerosis and antibody-mediated diseases of the central nervous system (COMMIT)

Sara Samadzadeh et al. Front Immunol. .

Abstract

Comorbidities in patients with multiple sclerosis (MS) and antibody-mediated diseases of the central nervous system (CNS) including neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOGAD) are common and may influence the course of their neurological disease. Comorbidity may contribute to neuronal injury and therefore limit recovery from attacks, accelerate disease progression, and increase disability. This study aims to explore the impact of comorbidity, particularly vascular comorbidity, and related risk factors on clinical and paraclinical parameters of MS, NMOSD and MOGAD. We propose COMMIT, a prospective multicenter study with longitudinal follow-up of patients with MS, NMOSD, and MOGAD, with or without comorbidities, as well as healthy subjects as controls. Subjects will be stratified by age, sex and ethnicity. In consecutive samples we will analyze levels of inflammation and neurodegeneration markers in both fluid and cellular compartments of the peripheral blood and cerebrospinal fluid (CSF) using multiple state-of-the-art technologies, including untargeted proteomics and targeted ultrasensitive ELISA assays and quantitative reverse transcription polymerase chain reaction (RT-qPCR) as well as high-dimensional single-cell technologies i.e., mass cytometry and single-cell RNA sequencing. Algorithm-based data analyses will be used to unravel the relationship between these markers, optical coherence tomography (OCT) and magnetic resonance imaging (MRI), and clinical outcomes including frequency and severity of relapses, long-term disability, and quality of life. The goal is to evaluate the impact of comorbidities on MS, NMOSD, and MOGAD which may lead to development of treatment approaches to improve outcomes of inflammatory demyelinating diseases of the CNS.

Keywords: antibody-mediated diseases of the central nervous system; comorbidity; multiple sclerosis; myelin oligodendrocyte glycoprotein antibody-associated disease; neuromyelitis optica spectrum disorder.

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Conflict of interest statement

STS as received personal fees from Munksgaard, TrustMe-Ed, and Nestlé Health Science outside the submitted work; is a co-founder of GLA:D®, a not-for-profit initiative hosted at the University of Southern Denmark aimed at implementing clinical guidelines for osteoarthritis in clinical practice; and has received a program grant from Region Zealand Exercise First and two grants from the European Union’s Horizon 2020 research and innovation program, one from the European Research Council MOBILIZE, grant agreement No. 801790 and the other under grant agreement No. 945377 ESCAPE. ML has received consulting fees and research grants from Alexion AstraZeneca, Horizon Amgen, and Genentech Roche. AP has received grant support for remyelination trials in multiple sclerosis from the Amsterdam University Medicam Centre, Department of Neurology, MS Centre RESTORE trial and UCL, London RECOVER trial and from Fight for Sight nimodipine in optic neuritis trial; has received royalties or licenses from UptoDate Wolters Kluwer on a book chapter and speaker fees from the Heidelberg Academy; has participated in the Advisory Board SC Zeiss OCTA Angi-Network; is the chairman of ERN-EYE Neuro-ophthalmology until OCT-2020 and a board member of the National Dutch Neuro-ophthalmology Association; and has received equipment OCTA from Zeiss Plex Elite. JP has received support for scientific meetings and honorariums for advisory work from Merck Serono, Novartis, Chugai, Alexion, Roche, Medimmune, Argenx, UCB, Mitsubishi, Amplo, Janssen, and Sanofi; grants from Alexion, Roche, Medimmune, UCB, and Amplo Biotechnology; and patent ref P37347WO and license agreement Numares multimarker MS diagnostics shares in AstraZeneca. She also acknowledges partial funding from the highly specialized services of NHS England. SMe has received travel grants from Merck, Roche, and Sanofi and speaking honoraria from UCB. RG has received support for scientific meetings and courses and honoraria for advisory work from Bayer, Biogen, Merck, Novartis, and Jasen. EF has served on advisory boards for Alexion, Genentech, Horizon Therapeutics, and UCB. He has received speaker honoraria from Pharmacy Times and royalties from UpToDate. He was a site primary investigator in a randomized clinical trial on inebilizumab in neuromyelitis optica spectrum disorder run by Medimmune/Viela-Bio/Horizon Therapeutics. He has received funding from the NIH R01NS113828 and is a member of the medical advisory board of the MOG project and an editorial board member of the Journal of the Neurological Sciences and Neuroimmunology Reports. SMa has received speaker honoraria from Biogen, Novartis, Horizon, and Sanofi. SA has received speaker’s honoraria from Alexion, Bayer, and Roche. HS-K has received support for scientific meetings from Roche. FO has received grants from the National Multiple Sclerosis Society US, American Academy of Neurology, Hertie Foundation for Excellence in Clinical Neuroscience, and Novartis—all independent of this project. HK has received a grant from the National Research Foundation of Korea and research support from AprilBio, Eisai, and UCB; has received consultancy/speaker fees from Alexion, Altos Biologics, AstraZeneca, Biogen, Daewoong Pharmaceutical, Eisai, GC Pharma, Handok Pharmaceutical, Kaigene, Kolon Life Science, MDimune, Merck Serono, Mitsubishi Tanabe Pharma, Roche, and Sanofi Genzyme; and is a co-editor for the Multiple Sclerosis Journal and an associated editor for the Journal of Clinical Neurology. MS and VS has received educational research grants, lecture honorarium, and travel support to attend scientific meetings from Biogen-Idec, Merck, Bayer, Novartis, Cinnagen, Osveh, Zistdaru, Zahravi, Abidi, and NanoAvland. JB reported personal fees from Roche, Genentech, Horizon, Chugai Pharma, Clene Nanoscience, Reistone-Bio, Beigene, and Imcyse; grants and personal fees from Alexion; and grants from the National Institutes of Health. JB has a patent aquaporumab issued. CB has received a grant from Roche, unrelated to this study. HZ has received grants from Novartis, unrelated to this study. BW has received royalties from RSR Ltd, Oxford University, Hospices Civil de Lyon, and MVZ Labor PD Dr. Volkmann und Kollegen GbR for a patent of NMO-IgG as a diagnostic test for neuromyelitis optica spectrum disorders; served on the adjudication committee for clinical trials conducted by MedImmune/VielaBio, Alexion, and UCB Biosciences; and consulted for Chugai/Roche/Genentech, Horizon Therapeutics, Mitsubishi-Tanabe, and CANbridge Pharmaceuticals regarding neuromyelitis optica spectrum disorders. He has received honoraria for speaking at internal meetings of Genentech, Novartis, and Horizon and at external meetings for Roche. FP served on the scientific advisory boards of Novartis and MedImmune; received travel funding and/or speaker honoraria from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an associate editor of Neurology: Neuroimmunology & Neuroinflammation; is an academic editor of PLoS ONE; consulted for Sanofi Genzyme, Biogen, MedImmune, Shire, and Alexion; received research support from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Alexion, and Merck Serono; and received research support from the German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy-Jackson Charitable Foundation, and NMSS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Timeline of patient assessments and interventions in a clinical study spanning 36 months.
See this image and copyright information in PMC

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