Investigation of Subclinical Markers of Multiple Sclerosis

ConditionsMultiple Sclerosis Relapsing Remitting Multiple Sclerosis

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18-65

SponsorUniversity of Split, School of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial population

Subjects with documented diagnosis of relapsing-remitting MS according to the McDonald criteria: Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Thompson AJ, et al. Lancet Neurol. 2018;17(2):162. Epub 2017 Dec 21

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

1. Clinical testing; 2. Neurophysiological examination (TMS, EMNG); 3. Psychomotor examination; 4. Neuropsychological evaluation; 5. Flow cytometry; 6. ELISA
Diagnostic test
All groups will not have the same intervention. Interventions are listed and numbered for each group.

Treatment groups

50 Participants

are divided into 3 treatment groups

Group A: Relapsing-remmitting MS group treated with corticosteroids1 intervention

Group B: Relapsing-remmitting MS group treated with immunomodulation1 intervention

Group C: Healthy control group1 intervention

Trial outcomes

Primary outcomes

TMS assessment of resting motor threshold (RMT) change

Neurophysiologic measure of RMT (expressed in percentage of maximal stimulator output) will be evaluated with navigated TMS over the primary motor cortex: * in relapsing-remitting MS receiving corticosteroid treatment patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * relapsing-remitting MS receiving immunomodulation treatment patients at baseline

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

The neurophysiologic measure of MEP (amplitude expressed in microvolts and latency expressed in milliseconds) will be evaluated with navigated TMS over the primary motor cortex for upper and lower extremity muscles: * in relapsing-remitting MS receiving corticosteroid treatment patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * relapsing-remitting MS receiving immunomodulation treatment patients at baseline

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

The neurophysiologic measure of CSP duration (expressed in milliseconds) will be evaluated with navigated TMS over the primary motor cortex in relapsing-remitting MS patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids).

Time frame

Baseline CSP, CSP change at 5 weeks taking the steroids

TMS assessment of short afferent latency inhibition (SAI) change

The neurophysiologic measure of SAI phenomena (expressed in milliseconds) will be evaluated with navigated TMS over the primary motor cortex with peripheral electrical stimulation over the median nerve at different interstimulus intervals (20-28 ms) in relapsing-remitting MS patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids).

Time frame

Baseline SAI, SAI change at 5 weeks after taking the steroids.

Secondary outcomes

-Detection of potential predictors (neurophysiological, neuropsychological, clinical neurological, clinical biochemical, and MRI measures) of medication treatment of relapsing-remitting MS.

Correlation and regression methods will be used to examine the following data: * neurophysiological data acquired with TMS (RMT; MEP; CSP; SAI); * neurophysiological data acquired with EMNG (DML and SNAP latency; CMAP and SNAP amplitude; motor and sensory CV; F-wave); * immunological data (expression profile of CD40, CD192, CD14, CD16 on monocytes and CD25, CTLA-4 and FOXP3 on lymphocytes; expression of CD163 in serum); * neuropsychological data; Edinburgh Handedness Inventory test; Pain rating scale; Barthel Index for Activities of Daily Living (ADL); FSS; LDST; MoCA; MSIS-29; DASS-21; O'Conner Finger Dexterity Test; muscle strength - hand grip and upper and lower extremity muscles with a dynamometer * clinical: EDSS,T25-FW; MRI; biochemical (complete blood count, differential blood count, AST, ALT, GGT, blood sugar test, creatinine, urine, B12, Na, K, Cl, folic acid, neurotrophic virus in serum and liquor, oligoclonal band)

Time frame

The complete data results will be provided at the end of the study.

Other outcomes

Neurological clinical assessment change with Expanded Disability Status Scale (EDSS).

* EDSS applied in relapsing-remiting MS patients before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. * EDSS applied in relapsing-remiting MS patients treated with immunomodulation at baseline. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.

Time frame

Baseline EDSS, and EDSS change at 5 weeks and 6 months after taking the steroids.

Neurological clinical assessment change with Timed 25-Foot Walk (T25-FW).

T25-FW applied in relapsing-remiting MS patients before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids.The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The score for the T25-FW is the average of the two completed trials.

Time frame

Baseline T25-FW, and T25-FW change at 5 weeks and 6 months after taking the steroids.

Clinical biochemical assessment change of complete blood count.

Clinical biochemical assessment of differential blood count will be provided before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. Following components of the blood are measured: leukocytes (x10\^9/L) (ref. interval. 3.4-9.7), erythrocytes (x10\^12/L) (ref. interval 3.86-5.08), haemoglobin (g/L) (ref. interval 119-157), hematocrit (L/L) (ref. interval 0.356-0.470), MCV (fL) (ref. interval 83.0-97.2), MCH (pg) (ref. interval 27.4-33.9), MCHC (g/L) (ref. interval 320-345), index of scattering of erythrocytes (%) (ref. interval 9.0-15.0), thrombocytes (x10\^9/L) (ref. interval 158-424), MPV (fL) (ref. interval 6.8-10.4), PDW (%) (ref. interval 35-65), PCT (L/L) (ref. interval 0.001-0.004)

Time frame

Baseline complete blood count, and blood coun change at 5 weeks and 6 months after taking the steroids.

Clinical biochemical assessment change of differential blood count.

Clinical biochemical assessment of differential blood count will be provided before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The blood collection is taken early in the morning, before breakfast. Following components of the blood are measured: neutrophile granulocytes (%) ( ref. interval 44-72), lymphocyte (%) (ref. interval 20-46), monocyte (%) (ref.interval 2-12), eosinophile (%) (ref. interval 0-7), basophile (%) (ref. interval 0-1), neutrophile # (x10\^9/L) (ref. interval 2.06-6.49), lymphocyte # (x10\^9/L) (ref. interval 1.19-3.35), monocyte # (x10\^9/L) (ref. interval 0.12-0.84), eosinophile # (x10\^9/L) (ref. interval 0.00-0.43), basophile # (x10\^9/L) (0.00-0.06)

Time frame

Baseline differential blood count, and differential blood count change at 5 weeks and 6 months after taking the steroids.

Sponsors and contacts

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University of Split, School of Medicine

Lead sponsor

University Hospital of Split

Collaborator

Source ClinicalTrials.gov

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