Clinical trial NCT04604041: Investigation of Subclinical Markers of Multiple Sclerosis
Official title: Investigation of Subclinical Markers of Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Relapsing Remitting Multiple Sclerosis
Keywords: multiple sclerosis
relapsing remitting
TMS
Cytometry
ELISA
corticosteroids
immunomodulation
Lead sponsor: University of Split, School of Medicine
Sponsor class: OTHER
Collaborators: name: University Hospital of Split
First posted: 2020-10-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study 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

Brief summary: 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.

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

Primary outcomes:
measure: TMS assessment of resting motor threshold (RMT) change
timeFrame: RMT before and 5 weeks after steroid intake in relapsing-remitting MS patients. RMT in relapsing-remitting MS group on immunomodulation.
measure: TMS assessment of motor evoked potentials (MEP) changes from upper and lower extremity muscles
timeFrame: 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.
measure: TMS assessment of cortical silent period (CSP) change
timeFrame: Baseline CSP, CSP change at 5 weeks taking the steroids
measure: TMS assessment of short afferent latency inhibition (SAI) change
timeFrame: Baseline SAI, SAI change at 5 weeks after taking the steroids.
measure: EMNG assessment of distal motor latency (DML) and sensory nerve action potential latency (SNAP) change
timeFrame: 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.
measure: EMNG assessment of muscle action potential amplitude (CMAP) and sensory nerve action potential amplitude (SNAP) change
timeFrame: 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.
measure: EMNG assessment of motor and sensory conduction velocity (CV) change
timeFrame: CV before and 5 weeks after steroid intake in relapsing-remitting MS patients. CV in relapsing-remitting MS group on immunomodulation.
measure: EMNG assessment of F-wave change
timeFrame: F-wave before and 5 weeks after steroid intake in relapsing-remitting MS patients. F-wave in relapsing-remitting MS group on immunomodulation.
measure: CD 14 expression on peripheral blood monocytes change
timeFrame: 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.
measure: CD 16 expression on peripheral blood monocytes change
timeFrame: 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.
measure: CD 40 expression on peripheral blood monocytes change
timeFrame: CD 40 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD 40 in relapsing-remitting MS group on immunomodulation and healthy control group.
measure: CD 192 expression on peripheral blood monocytes change
timeFrame: CD 192 before and 5 weeks after steroid intake in relapsing-remitting MS patients. CD 192 in relapsing-remitting MS group on immunomodulation and healthy control group.
measure: Change of CD 163 levels in blood serum samples
timeFrame: CD 163 measured before and 5 weeks after taking the steroids.
measure: CD 4 expression on lymphocytes
timeFrame: Determination of CD 4 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.
measure: CD 25 expression on lymphocytes
timeFrame: Determination of CD 25 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.
measure: CTLA-4 expression on lymphocytes
timeFrame: Determination of CTLA-4 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.
measure: FOXP3 expression on lymphocytes
timeFrame: Determination of FOXP3 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.
measure: Hand dominance assessment with Edinburgh Handedness Inventory test.
timeFrame: Baseline measurement for single subject. The results for all subjects can be provided an average of 1 year of study duration.
measure: Cognitive assessment change applying Letter Digit Substitution Test (LDST).
timeFrame: Baseline LDST, and LDST change at 5 weeks and 6 months after taking the steroids.
measure: Cognitive assessment change applying Montreal Cognitive Assessment (MoCA).
timeFrame: Baseline MoCA, and MoCA change at 5 weeks and 6 months after taking the steroids.
measure: Psychological assessment change applying Multiple Sclerosis Impact Scale (MSIS-29).
timeFrame: Baseline MSIS-29, and MSIS-29 change at 5 weeks and 6 months after taking the steroids.
measure: Psychological assessment change applying Depression, Anxiety, Stress (DASS-21) scale.
timeFrame: Baseline DASS-21, and DASS-21 change at 5 weeks and 6 months after taking the steroids.
measure: Psychological assessment change applying Fatigue Severity Scale (FSS).
timeFrame: Baseline FSS, and FSS change at 5 weeks and 6 months after taking the steroids.
measure: Psychological assessment change applying Pain rating scale.
timeFrame: Baseline Pain rating, and Pain rating change at 5 weeks and 6 months after taking the steroids.
measure: Psychomotor assessment of hand grip change applying SAEHAN Squeeze Dynamometer.
timeFrame: Baseline hand grip, and hand grip change at 5 weeks and 6 months after taking the steroids.
measure: Psychomotor assessment change of extremity muscles applying Lafayette Manual Muscle Tester Dynamometer.
timeFrame: Baseline lower and upper extremity muscle strength, and muscle strength change at 5 weeks and 6 months after taking the steroids.
measure: Psychomotor assessment change applying Lafayette O'Conner Finger Dexterity Test.
timeFrame: Baseline O'Conner, and O'Conner change at 5 weeks and 6 months after taking the steroids.
measure: Barthel Index for Activities of Daily Living (ADL) change.
timeFrame: Baseline activities of daily living, and change in activities of daily living at 5 weeks and 6 months after taking the steroids.
Secondary outcomes:
measure: -Detection of potential predictors (neurophysiological, neuropsychological, clinical neurological, clinical biochemical, and MRI measures) of medication treatment of relapsing-remitting MS.
timeFrame: The complete data results will be provided at the end of the study.
Other outcomes:
measure: Neurological clinical assessment change with Expanded Disability Status Scale (EDSS).
timeFrame: Baseline EDSS, and EDSS change at 5 weeks and 6 months after taking the steroids.
measure: Neurological clinical assessment change with Timed 25-Foot Walk (T25-FW).
timeFrame: Baseline T25-FW, and T25-FW change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of complete blood count.
timeFrame: Baseline complete blood count, and blood coun change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of differential blood count.
timeFrame: Baseline differential blood count, and differential blood count change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of glucose.
timeFrame: Baseline glucose, and glucose change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of urea.
timeFrame: Baseline urea, and urea change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of creatinine.
timeFrame: Baseline creatinine, and creatinine change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of Aspartate Aminotransferase (AST) Test.
timeFrame: Baseline AST, and AST change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of Alanine Aminotransferase (ALT) Test.
timeFrame: Baseline ALT, and ALT change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of Gamma-Glutamyl Transferase (GGT).
timeFrame: Baseline GGT, and GGT change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of urine.
timeFrame: Baseline urine, urine change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of B12.
timeFrame: Baseline B12, B12 change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of sodium (Na).
timeFrame: Baseline Na, Na change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of potassium (K).
timeFrame: Baseline K, K change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of chloride (Cl).
timeFrame: Baseline Cl, Cl change at 5 weeks and 6 months after taking the steroids.
measure: Clinical biochemical assessment change of folic acid (FA).
timeFrame: Baseline FA, and FA change at 5 weeks and 6 months after taking the steroids.
measure: Serologic test for neurotropic viruses and bacteria in blood serum and cerebrospinal liquor.
timeFrame: Baseline Serologic test for neurotropic viruses and bacteria in blood serum and cerebrospinal liquor.
measure: Microscopic and biochemical assessment of cerebrospinal liquor.
timeFrame: Baseline Microscopic and biochemical assessment of cerebrospinal liquor
measure: Oligoclonal bands in cerebrospinal liquor.
timeFrame: Baseline Oligoclonal bands in cerebrospinal liquor
measure: MRI radiological evaluation with contrast for detection of plaques and plaque location.
timeFrame: MRI scanning baseline and 6 months after the intake of steroids.
Locations:
city: Split
country: Croatia
facility: University of Split School of Medicine
Study officials:
affiliation: University of Split, School of Medicine
name: Maja Rogić Vidaković, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
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