Investigation of Subclinical Markers of Multiple Sclerosis

NCT ID: NCT04604041

Last Updated: 2023-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-11-23

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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Multiple Sclerosis Relapsing Remitting Multiple Sclerosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

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

Intervention Type DIAGNOSTIC_TEST

All groups will not have the same intervention. Interventions are listed and numbered for each group.

Relapsing-remmitting MS group treated with immunomodulation

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

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

Intervention Type DIAGNOSTIC_TEST

All groups will not have the same intervention. Interventions are listed and numbered for each group.

Healthy control group

5\. Flow cytometry

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

Intervention Type DIAGNOSTIC_TEST

All groups will not have the same intervention. Interventions are listed and numbered for each group.

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital of Split

OTHER

Sponsor Role collaborator

University of Split, School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Maja Rogić Vidaković

Research Associate Maja Rogić Vidaković

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Maja Rogić Vidaković, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Split, School of Medicine

Locations

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University of Split School of Medicine

Split, , Croatia

Site Status RECRUITING

Countries

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Croatia

Central Contacts

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Maja Rogić Vidaković, MSc, PhD

Role: CONTACT

0038598508210

Sanda Pavelin, MD, PhD

Role: CONTACT

Facility Contacts

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Lana Bošnjak, PhD

Role: primary

+385 21 557929

References

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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.

Reference Type BACKGROUND
PMID: 21387374 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6685237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32474916 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32029369 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29363161 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9916140 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29445750 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31637963 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29275977 (View on PubMed)

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.

Reference Type RESULT
PMID: 35054278 (View on PubMed)

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.

Reference Type RESULT
PMID: 34917005 (View on PubMed)

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.

Reference Type RESULT
PMID: 33636617 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40244940 (View on PubMed)

Other Identifiers

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003-08/20-03/0005

Identifier Type: OTHER

Identifier Source: secondary_id

2181-147-01/06/M.S.-20-2.

Identifier Type: OTHER

Identifier Source: secondary_id

500-03/20-01/06

Identifier Type: OTHER

Identifier Source: secondary_id

2181-198-03-04-20-0028.../0005

Identifier Type: -

Identifier Source: org_study_id

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