Exercise on Contactin-1 and Contactin-2 Level in Persons With Multiple Sclerosis

NCT ID: NCT05351411

Last Updated: 2022-04-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2022-03-04

Brief Summary

Little is known about the potential effects of exercise on the underlying disease mechanisms in multiple sclerosis (MS). Although contactin-1 and contactin-2 are known as two proteins involved in axonal regeneration, it is unclear whether these proteins are induced by exercise in persons with MS (PwMS). The aim of this study was to determine the serum levels of contactin-1 and contactin-2 in PwMS and to investigate the change of these markers with exercise. Although contactin-1 and contactin-2 are known as two proteins involved in axonal regeneration, the mechanism of action of these proteins in MS patients has not been fully elucidated in the literature. The investigators' aim was to determine the serum levels of contactin-1 and contactin-2 in a group of relapsing-remitting multiple sclerosis (RRMS) patients and to evaluate the change of these markers with exercise. Thus, the investigators think that a valuable contribution will be made to the literature to shed light on the role of biomarkers in the mechanism mediating the beneficial effects of exercise in MS. In addition, as far as the investigators know, this study is the first to investigate the effect of exercise on contactin-1 and contactin-2 serum levels in MS patients.

Detailed Description

This randomized controlled trial with a blinded outcome assessment evaluated an 8-week (3 sessions per week) training intervention to determine the effect of exercise on contactin-1 and contactin-2 in persons with RRMS. The participants were divided into the intervention and control groups by stratified randomization. Stratification was randomly assigned as 1≤ EDSS ≤ 3 and 3< EDSS ≤5.5 using Windows-based SPSS 25.0. (SPSS Inc., Chicago, Illinois, USA). All measurements and tests were performed before and after the 8-week exercise program. Blood samples were taken for analysis of contactin-1 and contactin-2 serum levels, after which participants completed a cognitive performance and a cardiopulmonary exercise test.

The current study was approved by the Fırat University Human Research Ethics Local Committee (2021/12-38) and was conducted in accordance with the Declaration of Helsinki. All participants were informed about the study and their written informed consent was obtained before the study. Participants performed a graded cardiopulmonary exercise test on a cycle ergometer (Ergoline Ergoselect 200; Ergoline GMBH, Bitz, Germany) at the beginning to determine their maximum aerobic capacity. The test was stopped at the moment of voluntary exhaustion, when patients were unable to maintain cadence (<50 rpm), the maximum effort was achieved, or for safety reasons. Venous blood was drawn using venipuncture and clotted for serum and centrifuged at 4000g for 5 minutes at 4°C. Serum samples then were aliquoted, and stored at -80°C until were assayed with enzyme-linked immunosorbent assay (ELISA) analysis. The serum levels of Contactin-1 (Cat.No: E-EL-H1498) and Contactin-2 (Cat.No: E-EL-H1499) were measured with commercially available specific human ELISA kits (Elabscience, Houston, Texas, United States). Paced Auditory Serial Addition Test with the 3-second stimulus (PASAT-3) was used as a measure of cognitive performance including information processing speed, working memory and sustained attention

Conditions

Relapsing Remitting Multiple Sclerosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

combined progressive functional exercise

The initial implementation for the 8-week (3 days per week) combined exercise program consisted of a progressive aerobic exercise program with a lower extremity bike. The second part of the combined exercise program, the progressive resistance training program, is designed to be consistent with the resistance training section of the Canadian Physical Activity Guidelines for adults with MS. Each prescribed session consisted of 1-3 sets and 10-15 repetitions of 10 exercises targeting major muscle groups of the upper and lower extremities. The specific exercises prescribed included lunges, chair raises/squats, calf raises, knee flexion, knee extensions, shoulder rows, shoulder lateral raises, elbow flexions, elbow extensions, and abdominal curls.

Intervention Type: OTHER

Participants in the control group maintained their therapeutic routine and had the opportunity to take part in the combined progressive functional exercise intervention after follow-up assessments had been conducted.

Placebo

Participants in the control group maintained their routine and had the opportunity to take part in the combined progressive functional exercise intervention after follow-up assessments had been conducted.

No interventions assigned to this group

Interventions

Participants in the control group maintained their therapeutic routine and had the opportunity to take part in the combined progressive functional exercise intervention after follow-up assessments had been conducted.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• definite diagnosis of RRMS according to the McDonalds criteria,
• 18 years or older,
• EDSS levels of 1.0 - 5.5, EDSS "pyramidal functions" sub score ≥2,
• who have not had an attack in the last 3 months,
• who were patients who did not receive steroid treatment for the last 3 months.

Exclusion Criteria

• orthopedic, cardiopulmonary, or systemic problems that prevent participation in exercises,
• pregnancy,
• started immunomodulatory treatment in the last 6 months,
• participated in resistance training 3 months before inclusion in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Firat University

OTHER

Sponsor Role: lead

Responsible Party

Furkan BİLEK

Lecturer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Caner F Demir, MD professor

Role: STUDY_DIRECTOR

Firat University

Locations

Fırat university

Elâzığ, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018 Apr 21;391(10130):1622-1636. doi: 10.1016/S0140-6736(18)30481-1. Epub 2018 Mar 23.

Reference Type: BACKGROUND

PMID: 29576504 (View on PubMed)

Negaresh R, Motl RW, Zimmer P, Mokhtarzade M, Baker JS. Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: a systematic review of intervention studies. Eur J Neurol. 2019 May;26(5):711-721. doi: 10.1111/ene.13929. Epub 2019 Mar 14.

Reference Type: BACKGROUND

PMID: 30734989 (View on PubMed)

Sandroff BM, Richardson EV, Motl RW. The Neurologist as an Agent of Exercise Rehabilitation in Multiple Sclerosis. Exerc Sport Sci Rev. 2021 Oct 1;49(4):260-266. doi: 10.1249/JES.0000000000000262.

Reference Type: BACKGROUND

PMID: 34049322 (View on PubMed)

Motl RW, Sandroff BM. Exercise as a Countermeasure to Declining Central Nervous System Function in Multiple Sclerosis. Clin Ther. 2018 Jan;40(1):16-25. doi: 10.1016/j.clinthera.2017.12.001. Epub 2017 Dec 26.

Reference Type: BACKGROUND

PMID: 29287750 (View on PubMed)

Schutzer SE, Angel TE, Liu T, Schepmoes AA, Xie F, Bergquist J, Vecsei L, Zadori D, Camp DG 2nd, Holland BK, Smith RD, Coyle PK. Gray matter is targeted in first-attack multiple sclerosis. PLoS One. 2013 Sep 10;8(9):e66117. doi: 10.1371/journal.pone.0066117. eCollection 2013.

Reference Type: BACKGROUND

PMID: 24039694 (View on PubMed)

Derfuss T, Parikh K, Velhin S, Braun M, Mathey E, Krumbholz M, Kumpfel T, Moldenhauer A, Rader C, Sonderegger P, Pollmann W, Tiefenthaller C, Bauer J, Lassmann H, Wekerle H, Karagogeos D, Hohlfeld R, Linington C, Meinl E. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8302-7. doi: 10.1073/pnas.0901496106. Epub 2009 Apr 28.

Reference Type: RESULT

PMID: 19416878 (View on PubMed)

Shimoda Y, Watanabe K. Contactins: emerging key roles in the development and function of the nervous system. Cell Adh Migr. 2009 Jan-Mar;3(1):64-70. doi: 10.4161/cam.3.1.7764. Epub 2009 Jan 6.

Reference Type: RESULT

PMID: 19262165 (View on PubMed)

Colakoglu G, Bergstrom-Tyrberg U, Berglund EO, Ranscht B. Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):E394-403. doi: 10.1073/pnas.1313769110. Epub 2014 Jan 2.

Reference Type: RESULT

PMID: 24385581 (View on PubMed)

Dalgas U, Ingemann-Hansen T, Stenager E. Physical Exercise and MS Recommendations. Int MS J. 2009 Apr;16(1):5-11.

Reference Type: RESULT

PMID: 19413920 (View on PubMed)

Ocklenburg S, Gerding WM, Arning L, Genc E, Epplen JT, Gunturkun O, Beste C. Myelin Genes and the Corpus Callosum: Proteolipid Protein 1 (PLP1) and Contactin 1 (CNTN1) Gene Variation Modulates Interhemispheric Integration. Mol Neurobiol. 2017 Dec;54(10):7908-7916. doi: 10.1007/s12035-016-0285-5. Epub 2016 Nov 18.

Reference Type: RESULT

PMID: 27864734 (View on PubMed)

Other Identifiers

FıratUniversit

Identifier Type: -

Identifier Source: org_study_id