Investigation of Subclinical Markers of Multiple Sclerosis

NCT04604041 | Recruiting DMC

• 4 other identifiers: 2181-198-03-04-20-0028.../0005003-08/20-03/00052181-147-01/06/M.S.-20-2.500-03/20-01/06
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis

Keywords

multiple sclerosis; relapsing remitting; TMS; Cytometry; ELISA; corticosteroids; immunomodulation

Outcome Measures

Primary Outcomes (28)

• 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

  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

  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).

  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).

  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

  * EMNG measures of DML and SNAP latency (expressed in milliseconds) of upper and lower extremities will be evaluated in relapsing-remitting MS patients receiving corticosteroid treatment in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * EMNG measures of DML and SNAP latency (expressed in milliseconds) of upper and lower extremities will be evaluated in relapsing-remitting MS receiving immunomodulation treatment patients at baseline.

  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

  * EMNG measures of CMAP and SNAP amplitude (expressed in millivolts) of upper and lower extremities will be evaluated in relapsing-remitting MS patients receiving corticosteroid treatment in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * EMNG measures of CMAP and SNAP amplitude (expressed in millivolts) of upper and lower extremities will be evaluated in relapsing-remitting MS patients receiving immunomodulation treatment at baseline.

  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

  * EMNG measures of CV (expressed in meters per second) of motor and sensory nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). * EMNG measures of CV (expressed in meters per second) of motor and sensory nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with immunomodulation treatment at baseline.

  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

  -EMNG measures of F-wave (expressed in milliseconds) for motor nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). --EMNG measures of F-wave (expressed in milliseconds) for motor nerves of upper and lower extremities will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline.

  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

  * CD 14 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 14 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline.The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 14 expression on monocytes will be evaluated in the healthy control group.The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes.

  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

  * CD 16 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 16 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 16 expression on monocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes.

  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.

• CD 40 expression on peripheral blood monocytes change

  * CD 40 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, and 5 weeks after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 40 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 40 expression on monocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes.

  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.

• CD 192 expression on peripheral blood monocytes change

  * CD 192 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with corticosteroids in 2 phases (before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids). The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 192 expression on monocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes. * CD 192 expression on monocytes will be evaluated in a healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive monocytes

  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.

• Change of CD 163 levels in blood serum samples

  CD 163 levels in serum will be evaluated in relapsing-remitting MS patients in 2 phases (before the intake of steroids, 5 weeks after taking the steroids). CD 163 levels will be measured with ELISA assay (expressed in micro mols per litre).

  CD 163 measured before and 5 weeks after taking the steroids.

• CD 4 expression on lymphocytes

  * CD 4 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * CD 4 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

  Determination of CD 4 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

• CD 25 expression on lymphocytes

  * CD 25 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * CD 25 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

  Determination of CD 25 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

• CTLA-4 expression on lymphocytes

  * CTLA-4 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * CTLA-4 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

  Determination of CTLA-4 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

• FOXP3 expression on lymphocytes

  * FOXP3 expression on lymphocytes will be evaluated in relapsing-remitting MS patients treated with immunomodulation at baseline. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes. * FOXP3 expression on lymphocytes will be evaluated in the healthy control group. The expression will be measured as the median of fluorescence distribution acquired with flow cytometry. The expression will also be quantified as the percentage of positive lymphocytes.

  Determination of FOXP3 at the beginning of study (study entry) in relapsing-remitting MS patients treated with immunomodulation and in healthy control group.

• Hand dominance assessment with Edinburgh Handedness Inventory test.

  The Edinburgh Handedness Inventory is a well known short questionnaire for determining objectively whether one is left , right handed, or ambidekster. The subjects determines whether he/she is using right or left hand for specific activities (ten activities). The total checks are given for right and left hand, than cumulative sume is given (total checks from right and left hand), difference between total checks for right minus left hand. Final result is the difference result subtracted from cumulative result x 100.

  Baseline measurement for single subject. The results for all subjects can be provided an average of 1 year of study duration.

• Cognitive assessment change applying Letter Digit Substitution Test (LDST).

  * Relapsing-remitting MS patients treated with corticosteroids will be tested with LDST before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. LDST is interpreted as the number of correct responses in 60 seconds. * Relapsing-remitting MS patients treated with immunomodulation therapy will be tested with LDST at baseline.

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

• Cognitive assessment change applying Montreal Cognitive Assessment (MoCA).

  Relapsing-remitting MS patients will be tested with MoCA before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. MoCA is interpreted as the number of points (30 is maximal).

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

• Psychological assessment change applying Multiple Sclerosis Impact Scale (MSIS-29).

  * Relapsing-remitting MS patients treated with corticosteroids will be tested with MSIS before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The total score is formed as the sum of the rounded answers to the two subscales (physical and psychological scale). * Relapsing-remitting MS patients treated with immunomodulation will be tested with MSIS at baseline. The total score is formed as the sum of the rounded answers to the two subscales (physical and psychological scale).

  Baseline MSIS-29, and MSIS-29 change at 5 weeks and 6 months after taking the steroids.

• Psychological assessment change applying Depression, Anxiety, Stress (DASS-21) scale.

  * Relapsing-remitting MS patients treated with corticosteroids will be tested with DASS-21 before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. * Relapsing-remitting MS patients treated with immunomodulation will be tested with DASS-21 at baseline. DASS-21 contains three scales for measuring emotional states of depression, anxiety and stress. Each scale contains 7 statements. The result on the depression, anxiety and stress scales is the sum of the rounded answers to specific statements.

  Baseline DASS-21, and DASS-21 change at 5 weeks and 6 months after taking the steroids.

• Psychological assessment change applying Fatigue Severity Scale (FSS).

  -Relapsing-remitting MS patients treated with corticosteroids will be tested with FSS before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. --Relapsing-remitting MS patients treated with immunomodulation will be tested with FSS at baseline. The subject is asked to read each statement and circle a number from 1 to 7, depending on how appropriate they felt the statement applied to them over the preceding week. A low value indicates that the statement is not very appropriate whereas a high value indicates agreement.The scoring is done by calculating the average response to the questions (adding up all the answers and dividing by nine).

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

• Psychological assessment change applying Pain rating scale.

  Relapsing-remitting MS patients will be tested with numerical Pain Rating Scale before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The result is interpreted as the total sum of points. The greater the results the more pain is detected.

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

• Psychomotor assessment of hand grip change applying SAEHAN Squeeze Dynamometer.

  Relapsing-remitting MS patients will be tested with SAEHAN Squeeze Dynamometer before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. Six measurement results are recorded for each subject - three for the grip with the dominant hand and three for the grip with the non-dominant hand. The final result is the mean of the three measurements for each arm expressed in kilograms.

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

• Psychomotor assessment change of extremity muscles applying Lafayette Manual Muscle Tester Dynamometer.

  Relapsing-remitting MS patients will be tested with Lafayette Manual Muscle Tester Dynamometer before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. Muscle strength measured by Lafayette Manual Muscle Tester is recorded in kilograms and normalized to body-mass index (BMI). Handheld dynamometry will be used to measure ankle dorsiflexion; knee, flexion and extension; hip flexion, extension, abduction, and adduction; and trunk lateral flexion.

  Baseline lower and upper extremity muscle strength, and muscle strength change at 5 weeks and 6 months after taking the steroids.

• Psychomotor assessment change applying Lafayette O'Conner Finger Dexterity Test.

  Relapsing-remitting MS patients will be tested with O'Conner Finger Dexterity Test before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The O'Connor Finger Dexterity Test requires hand placement of 3 pins per hole. Result (seconds) = time required to complete the first part of the test + (1.1 x time required to complete the second part of the test) / 2

  Baseline O'Conner, and O'Conner change at 5 weeks and 6 months after taking the steroids.

• Barthel Index for Activities of Daily Living (ADL) change.

  Relapsing-remitting MS patients will be tested with Barthel Index for Activities of Daily Living (ADL) before the intake of steroids, 5 weeks after taking the steroids and 6 months after taking the steroids. The examiner is rank the patient's independence in the following areas:feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers (bed to chair and back), mobility on level surfaces, and stairs. \* 0 - 20 = complete dependence; 21 - 60 = severe addiction; 61 - 90 = moderate dependence

  Baseline activities of daily living, and change in activities of daily living at 5 weeks and 6 months after taking the steroids.

Secondary Outcomes (1)

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

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

Other Outcomes (20)

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

  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).

  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.

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

Study Arms (3)

Relapsing-remmitting MS group treated with corticosteroids

1. Clinical testing 2. Neurophysiological examination (TMS, EMNG) 3. Psychomotor examination 4. Neuropsychological evaluation 5. Flow cytometry 6. ELISA

Diagnostic Test: 1. Clinical testing; 2. Neurophysiological examination (TMS, EMNG); 3. Psychomotor examination; 4. Neuropsychological evaluation; 5. Flow cytometry; 6. ELISA

Relapsing-remmitting MS group treated with immunomodulation

1\. Clinical testing 2. Neurophysiological examination (TMS, EMNG) 4. Neuropsychological evaluation 5. Flow cytometry

Diagnostic Test: 1. Clinical testing; 2. Neurophysiological examination (TMS, EMNG); 3. Psychomotor examination; 4. Neuropsychological evaluation; 5. Flow cytometry; 6. ELISA

Healthy control group

5\. Flow cytometry

Diagnostic Test: 1. Clinical testing; 2. Neurophysiological examination (TMS, EMNG); 3. Psychomotor examination; 4. Neuropsychological evaluation; 5. Flow cytometry; 6. ELISA

Interventions

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.

Healthy control group; Relapsing-remmitting MS group treated with corticosteroids; Relapsing-remmitting MS group treated with immunomodulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Split, School of Medicine: lead
• University Hospital of Split: collaborator

Study Sites (1)

University of Split School of Medicine

Split, 21000, Croatia

RECRUITING

Related Publications (13)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.

  PMID: 29275977 BACKGROUND

• Jerkovic A, Matijaca M, Prorokovic A, Sikic A, Kosta V, Curkovic Katic A, Dolic K, Duka Glavor K, Soda J, Dogas Z, Rogic Vidakovic M. Information Processing Speed Assessed with Letter Digit Substitution Test in Croatian Sample of Multiple Sclerosis Patients. Diagnostics (Basel). 2022 Jan 4;12(1):111. doi: 10.3390/diagnostics12010111.

  PMID: 35054278 RESULT

• Jerkovic A, Prorokovic A, Matijaca M, Vuko J, Poljicanin A, Mastelic A, Curkovic Katic A, Kosta V, Kustura L, Dolic K, Ethogas Z, Rogic Vidakovic M. Psychometric Properties of the HADS Measure of Anxiety and Depression Among Multiple Sclerosis Patients in Croatia. Front Psychol. 2021 Nov 30;12:794353. doi: 10.3389/fpsyg.2021.794353. eCollection 2021.

  PMID: 34917005 RESULT

• Rogic Vidakovic M, Simic N, Poljicanin A, Nikolic Ivanisevic M, Ana J, Dogas Z. Psychometric properties of the Croatian version of the depression, anxiety, and stress scale-21 and multiple sclerosis impact scale-29 in multiple sclerosis patients. Mult Scler Relat Disord. 2021 May;50:102850. doi: 10.1016/j.msard.2021.102850. Epub 2021 Feb 20.

  PMID: 33636617 RESULT

• Bralic A, Pavelin S, Pleic N, Soda J, Dolic K, Markotic A, Curkovic Katic A, Mastelic A, Rezic Muzinic N, Duranovic J, Kljajic Z, Stipica Safic I, Dogas Z, Rogic Vidakovic M. Correspondence of MRI and nTMS With EDSS in Multiple Sclerosis: Longitudinal Follow-Up Study. Ann Clin Transl Neurol. 2025 Jun;12(6):1240-1255. doi: 10.1002/acn3.70041. Epub 2025 Apr 17.

  PMID: 40244940 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum of study participants will be banked for future possible retrospective analysis.

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Maja Rogić Vidaković, MSc, PhD

  University of Split, School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maja Rogić Vidaković, MSc, PhD

CONTACT

0038598508210; maja.rogic@mefst.hr

Sanda Pavelin, MD, PhD

CONTACT

spavelin@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Associate Maja Rogić Vidaković

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 27, 2020
• Study Start: November 23, 2020
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 2, 2023

Record last verified: 2023-09

Locations

CR (1)