Investigation of Subclinical Markers of Multiple Sclerosis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: 1. Clinical testing; 2. Neurophysiological examination (TMS, EMNG); 3. Psychomotor examination; 4. Neuropsychological evaluation; 5. Flow cytometry; 6. ELISA.
- Who it may be relevant to
- Registry conditions: Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Croatia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
Transcranial magnetic stimulation (TMS) studies reported consistent and substantial impairments in the central nervous system (CNS) in multiple sclerosis (MS). Studies of peripheral nervous system (PNS) function comprising electromyoneurography (EMNG) reported impairments of the PNS in MS that were less pronounced and inconsistent. Neurophysiological studies are generally small and cross-sectional and with the poor grouping of MS patients according to MS type. The objective of the study is to investigate clinical, neurophysiological, and immunological markers in relapsing-remitting MS patients, and in patients with relapsing-remitting MS treated with immunomodulation. The results of the study may contribute to a better understanding of the pathophysiology of multiple sclerosis and can provide guidance in the diagnosis and treatment of patients with relapsing-remitting MS.
Detailed description
The following techniques will be applied:
* Neurophysiological testing will be performed with navigated transcranial magnetic stimulation (nTMS) incorporating an individual MRI of each subject's brain performed on a 1,5 MRI scanner using a series of neuropsychological protocols. Mapping of the primary motor cortex for upper and lower extremity muscles with a recording of motor evoked potentials (MEP) will be performed. * Electromyoneurography (EMNG) assessment of lower and upper extremities for motor and sensory nerves; * Neuropsychological assessment will include the general questionnaire and battery of cognitive and psychological tests; * Immunoassays on blood samples include determination of different markers on monocytes and lymphocytes using flow cytometry, as well as determination of CD163 in serum samples using ELISA. * Clinical examinations include neurological, biochemical, neuroradiological, and neuropsychological testing.
Interventions
- Diagnostic test 1. Clinical testing; 2. Neurophysiological examination (TMS, EMNG); 3. Psychomotor examination; 4. Neuropsychological evaluation; 5. Flow cytometry; 6. ELISA
All groups will not have the same intervention. Interventions are listed and numbered for each group.
Primary outcome measures
- TMS assessment of resting motor threshold (RMT) change [Time frame: RMT before and 5 weeks after steroid intake in relapsing-remitting MS patients. RMT in relapsing-remitting MS group on immunomodulation.]
- TMS assessment of motor evoked potentials (MEP) changes from upper and lower extremity muscles [Time frame: MEP (amplitude and latency) before and 5 weeks after steroid intake in relapsing-remitting MS patients. MEP (amplitude and latency) in relapsing-remitting MS group on immunomodulation.]
- TMS assessment of cortical silent period (CSP) change [Time frame: Baseline CSP, CSP change at 5 weeks taking the steroids]
- TMS assessment of short afferent latency inhibition (SAI) change [Time frame: Baseline SAI, SAI change at 5 weeks after taking the steroids.]
- EMNG assessment of distal motor latency (DML) and sensory nerve action potential latency (SNAP) change [Time frame: DML and SNAP latency before and 5 weeks after steroid intake in relapsing-remitting MS patients. DML and SNAP latency in relapsing-remitting MS group on immunomodulation.]
- EMNG assessment of muscle action potential amplitude (CMAP) and sensory nerve action potential amplitude (SNAP) change [Time frame: CMAP and SNAP amplitude before and 5 weeks after steroid intake in relapsing-remitting MS patients. CMAP and SNAP amplitude in relapsing-remitting MS group on immunomodulation.]
- EMNG assessment of motor and sensory conduction velocity (CV) change [Time frame: CV before and 5 weeks after steroid intake in relapsing-remitting MS patients. CV in relapsing-remitting MS group on immunomodulation.]
- EMNG assessment of F-wave change [Time frame: F-wave before and 5 weeks after steroid intake in relapsing-remitting MS patients. F-wave in relapsing-remitting MS group on immunomodulation.]
- CD 14 expression on peripheral blood monocytes change [Time frame: CD 14 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD14 in relapsing-remitting MS group on immunomodulation and healthy control group.]
- CD 16 expression on peripheral blood monocytes change [Time frame: CD 16 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD16 in relapsing-remitting MS group on immunomodulation and healthy control group.]
Secondary outcome measures (1)
- -Detection of potential predictors (neurophysiological, neuropsychological, clinical neurological, clinical biochemical, and MRI measures) of medication treatment of relapsing-remitting MS. [Time frame: The complete data results will be provided at the end of the study.]
Eligibility criteria
Inclusion criteria
- Subjects with a documented diagnosis of relapsing-remitting MS according to the Mc Donald criteria (2005) and with EDSS achievement of 0-3.5 according to the modified Kurtzke's EDSS (Expanded disability status scale) for the assessment of neurological function and incapacity of patients with multiple sclerosis
Exclusion criteria
- Patients with metals in the body (e.g. pacemaker, dentures)
- Patients with new pregnancies (verbally confirmed)
- Patients with new head trauma
- Subjects unwilling to sign a consent or follow study procedures
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Study design
- Observational model
- Cohort
Study locations
Croatia · 1 center
- University of Split School of Medicine — Split
Publications
- Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366. PMID 21387374
- 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
- Mamoei S, Hvid LG, Boye Jensen H, Zijdewind I, Stenager E, Dalgas U. Neurophysiological impairments in multiple sclerosis-Central and peripheral motor pathways. Acta Neurol Scand. 2020 Nov;142(5):401-417. doi: 10.1111/ane.13289. Epub 2020 Jun 23. PMID 32474916
- Gorgulu U, Ergun U, Ertugrul L. Peripheral nerve conductions in relapsing remitting multiple sclerosis (RRMS) patients. J Clin Neurosci. 2020 Apr;74:93-97. doi: 10.1016/j.jocn.2020.01.058. Epub 2020 Feb 3. PMID 32029369
- Gjelstrup MC, Stilund M, Petersen T, Moller HJ, Petersen EL, Christensen T. Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis. Immunol Cell Biol. 2018 Feb;96(2):160-174. doi: 10.1111/imcb.1025. Epub 2017 Dec 11. PMID 29363161
- Howard LM, Miga AJ, Vanderlugt CL, Dal Canto MC, Laman JD, Noelle RJ, Miller SD. Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple sclerosis. J Clin Invest. 1999 Jan;103(2):281-90. doi: 10.1172/JCI5388. PMID 9916140
- Kawarabayashi R, Motoyama K, Nakamura M, Yamazaki Y, Morioka T, Mori K, Fukumoto S, Imanishi Y, Shioi A, Shoji T, Emoto M, Inaba M. The Association between Monocyte Surface CD163 and Insulin Resistance in Patients with Type 2 Diabetes. J Diabetes Res. 2017;2017:6549242. doi: 10.1155/2017/6549242. Epub 2017 Dec 28. PMID 29445750
- Wojcik CM, Beier M, Costello K, DeLuca J, Feinstein A, Goverover Y, Gudesblatt M, Jaworski M 3rd, Kalb R, Kostich L, LaRocca NG, Rodgers JD, Benedict RH; National MS Society Cognition Work Team. Computerized neuropsychological assessment devices in multiple sclerosis: A systematic review. Mult Scler. 2019 Dec;25(14):1848-1869. doi: 10.1177/1352458519879094. Epub 2019 Oct 22. PMID 31637963
Identifiers
NCT: NCT04604041 · 2181-198-03-04-20-0028.../0005 · 003-08/20-03/0005 · 2181-147-01/06/M.S.-20-2. · 500-03/20-01/06