Investigation of Subclinical Markers of Multiple Sclerosis

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест 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.

Первичные конечные точки

• TMS assessment of resting motor threshold (RMT) change [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline CSP, CSP change at 5 weeks taking the steroids]
• TMS assessment of short afferent latency inhibition (SAI) change [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Вторичные конечные точки (1)

• -Detection of potential predictors (neurophysiological, neuropsychological, clinical neurological, clinical biochemical, and MRI measures) of medication treatment of relapsing-remitting MS. [Срок оценки: The complete data results will be provided at the end of the study.]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Хорватия · 1 центр

• University of Split School of Medicine — Split

Публикации

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• 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
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• 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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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