- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04121637
To Investigate the Effect of Aerobic Exercise on Neurophysiological Values and Functionality in Individuals With Multiple Sclerosis.
Multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system, is characterized by myelin, oligodendrocytes and axon damage.
Physical exercises can be beneficial to patients, reduce fatigue and improve their strength, endurance and quality of life. Exercise has the potential to improve and / or preserve functionality, aerobic condition, strength, fatigue, health-related quality of life, depression, and cognition in MS patients. It has been reported that aerobic exercise increases muscle strength and endurance in peak oxygen intake and decreases fatigue and improves activity level, balance and walking patterns.
It is important to control the problems caused by ataxia in MS patients, to improve balance and postural reactions and to increase proximal muscle and trunk stabilization. For this purpose, movements are voluntarily and graded. Progress in exercises is achieved by making changes in the speed, width and complexity of movement. However, Frenkel Coordination exercises for extremity ataxia are usually included in the physiotherapy and rehabilitation program.
Little is known about the role and function of the iris in the nervous system with the discovery of Irisin and its precursor protein FNDC5. Evidence that the plasma level of iris increases during physical exercise suggests that it may also have beneficial and neuroprotective effects in the brain. Increased physical exercise has been shown to be associated with FNDC5 expression and ultimately more secretion of the iris.
The effect of elevated plasma iris levels after aerobic exercise on functionality in MS patients is unknown. Moon et al. Observed that cellular proliferation in mouse hippocampus cells was dose-dependent due to iris. In spraque dawley-type male rats, the presence of significant iris in the myelin sheath of the skeletal muscle shows that this tissue is an important source of iris. Based on these findings, it is thought that exercise-induced iris, which is an important cause of disability in MS, may have beneficial effects on the recovery of normal function in these patients. Whether iris affects nerve conduction velocity will be determined by electromyography analysis before and after aerobic exercise. In addition, the relationship between aerobic exercise and motor and sensory function and iris will be investigated and evaluated with functional tests.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Purpose of the research:
The aim of this study is to investigate the effect of aerobic exercise on neurophysiological values and functionality in individuals with multiple sclerosis.
The aim of this study is to determine whether aerobic exercise has positive effects on neurophysiological values and functionality in MS patients and to investigate this in a multidisciplinary and multidisciplinary manner.
Materials and Methods:
Patients with MS who were referred to the physiotherapy and rehabilitation program by the Physical Medicine and Rehabilitation specialist at Fırat University Training and Research Hospital will be included in the study.
In this study, patients with MS will be divided into two groups by stratified randomization method. Stratification will be performed in the early period of MS (EDSS 0.5-2.5) and in the late period of MS (EDSS 3-5.5). For a total of 18 sessions, only Frenkel Coordination exercises will be done to the control group, and Frenkel Coordination exercises and aerobic exercise will be applied to the study group.
Physiotherapy and Rehabilitation Program Control Group: Patients will receive Frenkel Coordination exercises (4 different exercises 4-5 repetitions depending on the individual's functional and motor status) for 6 weeks. There will be a 1 minute break between each exercise set.
Study Group: Patients will receive Frenkel Coordination exercises (4 different exercises 4-5 repetitions depending on the individual's functional and motor status) for 6 weeks. There will be a 1 minute break between each exercise set. Following this, an aerobic exercise of 30 minutes will be performed on the bicycle ergometer with electronic brake. Subjects will be advised not to do any exercise two days before or on that day and to eat only a light meal at least two hours before the test. The intensity of the exercise will be adjusted based on maximum oxygen consumption (VO2 max) specific to each individual.
Each exercise session;
- 5 min warm-up = 30% of VO2 max
- 20 min exercise = 50-60% of VO2 max
- 5 minutes cooling in the form. The goal of aerobic exercise is to increase physical capacity, which is represented by maximum oxygen uptake (VO2max) and mechanical power generated during exercise. Training programs should be conducted at least 2 to 3 times per week (60-80% maximum work rate or 60% VO2max) for 30 to 60 minutes at moderate concentrations. These programs are effective in increasing aerobic capacity and power output in MS (16).
Oxygen consumption (VO2), exhaled carbon dioxide (VCO2), minute ventilation (VE), respiratory rate (RR), respiration change rate (RER) and oxygen saturation (SaO2) will be recorded.
Evaluation Protocol:
Electromyography (EMG), max VO2 values and iris levels are analyzed before and after treatment and scales and questionnaires will be applied to evaluate the functional levels.
Within the scope of EMG evaluation, motor and sensory conduction studies of ulnar and median nerve in upper extremity, peroneal and tibial nerve in lower extremity, F response and H-reflex study in motor nerves, sensory conduction study of sural nerve in lower extremity are planned. H reflex is a monosynaptic reflection carried by 1a sensory fibers that synapse with alpha motor neuron. Response F shows the repeated discharges of alpha motor neurons and is a test used for the evaluation of diseases that cause transmission slowdown.
The VO2 max measurement will be performed using the incremental exercise test to determine the maximum aerobic capacity. After resting for 5 minutes (sitting on the ergometer), patients will be asked to start cycling on the ergometer starting at 25W. The load will be increased by 25W every 3 minutes until depletion. Subjects will be encouraged to continue the exercise as much as possible orally. Oxygen consumption (VO2), exhaled carbon dioxide (VCO2), minute ventilation (VE), respiration rate (RR), respiration change rate (RER), oxygen saturation (SaO2) and heart rate will be recorded. In the statistical analysis, only VO2 max values will be examined.
For the analysis of the level of iris, blood samples will be taken from gel biochemistry tubes as appropriate for the analyzes to be performed from the patients at the end of the aerobic capacity assessment. Blood samples will be separated by centrifugation at 3000rpm for 10min and the obtained sera will be placed in small portions in ependorf tubes and stored at -80 ° C until analysis. Irisin levels will be studied using commercial ELISA (enzyme-linked immunosorbent assay) kits in accordance with the kit user manual.
Multiple Sclerosis Functional Composite (MSFC), Ataxia Assessment and Rating Scale (SARA), Modified Borg Scale (MBS) to determine the effect of aerobic exercise on functionality in individuals with MS , Fatigue Impact Scale (FIS), Leeds Multiple Sclerosis Quality of Life Scale (Leeds Multiple Sclerosis Quality of L)
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Furkan BİLEK, Ph. D.
- Phone Number: 0090 5442772249
- Email: fzt.furkanbilek@gmail.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- EDSS score in the range of 0.5-5.5,
- Patients with relapsing-remitting type MS
- Patients diagnosed with MS who did not receive steroid therapy or were discontinued 3 months before starting the study.
Exclusion Criteria:
- Has an acute MS attack or has a history of attacks in the last 3 months,
- Have orthopedic or systemic problems to prevent participation in the exercises,
- Another known neuromuscular disorder other than MS,
- Immunomodulatory therapy started in the last 6 months,
- Have visual involvement or diplopia,
- Upper spasticity of lower limbs (Ashworth score 3 or 4),
- Patients with cardio-pulmonary problems that would prevent their participation in the exercise.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Aerobic exercise+Frenkel coordination Study group
Patients will be given Frenkel Coordination exercises (4 different exercises 4-5 repetitions depending on the individual's functional and motor status) 3 times a week for 6 weeks.
There will be a 1 minute break between each exercise set.
Following this, an aerobic exercise of 30 minutes will be performed on the bicycle ergometer with electronic brake.
Subjects will be advised not to do any exercise two days before or on that day and to eat only a light meal at least two hours before the test.
The intensity of the exercise will be adjusted based on maximum oxygen consumption (VO2 max) specific to each individual.
|
Each exercise session;
Patients will be given Frenkel Coordination exercises (4 different exercises 4-5 repetitions depending on the individual's functional and motor status) 3 times a week for 6 weeks. 1 minute break between each exercise set
|
Active Comparator: Frenkel coordination exercise group - Control group
Patients will be given Frenkel Coordination exercises (4 different exercises 4-5 repetitions depending on the individual's functional and motor status) 3 times a week for 6 weeks.
There will be a 1 minute break between each exercise set.
|
Patients will be given Frenkel Coordination exercises (4 different exercises 4-5 repetitions depending on the individual's functional and motor status) 3 times a week for 6 weeks. 1 minute break between each exercise set
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Physiological - Irisin Hormone
Time Frame: 8 mounth
|
For the analysis of the level of iris, blood samples will be taken from gel biochemistry tubes as appropriate for the analyzes to be performed from the patients at the end of the aerobic capacity assessment.
Blood samples will be separated by centrifugation at 3000rpm for 10min and the obtained sera will be placed in small portions in ependorf tubes and stored at -80 ° C until analysis.
Irisin levels will be studied in accordance with the kit user manual using commercial ELISA (enzyme-linked immunosorbent assay) kits
|
8 mounth
|
Neurophysiological - EMG
Time Frame: 8 mounth
|
In the scope of EMG evaluation, the motor and sensory conduction studies of the ulnar and median nerve in the upper extremity, the peroneal and tibial nerves in the lower extremity, the F response and H-reflex study in the motor nerves, and the sensory conduction study of the sural nerve in the lower extremity are planned.
|
8 mounth
|
VO2 Max
Time Frame: 8 mounth
|
The VO2 max measurement will be performed using the incremental exercise test to determine the maximum aerobic capacity.
After resting for 5 minutes (sitting on the ergometer), patients will be asked to start cycling on the ergometer starting at 25W.
The load will be increased by 25W every 3 minutes until depletion.
|
8 mounth
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Multiple Sclerosis Functional Composites (MSFC)
Time Frame: 8 mounth
|
Multiple Sclerosis Functional Composites (MSFC) was developed by the National MS Society's Clinical Outcomes Assessment Task Force.
Objective assessment of functional disability score and help to maintain the standard of patient follow-up.
It consists of 25 Step Walk Test, 9 Hole Peg Test, Step Auditory Serial Addition Test (PASAT) subtests.
PASAT is used to measure the speed of auditory information processing, computational skills and attention from executive functions.
It has two forms, A and B, and is performed with a standard voice recording.
Each form has two subtests.
In the first subtest, the numbers are repeated at three-second intervals, and the patient is expected to add the next number he heard.
Each time, the patient must add the previous and the new number.
9 Perforated Peg Test is a test that measures upper extremity functions (hand and arm) and motor speed.
|
8 mounth
|
Ataxia Scale (SARA)
Time Frame: 8 mounth
|
The Ataxia Scale (SARA) is a scale used to assess ataxia including clinical dysfunction, limb movements, kinetic functions, posture and gait disorders, speech and oculomotor disorders.
SARA subscores are posture and gait, speech, kinetic functions of the extremities
|
8 mounth
|
Leeds Multiple Sclerosis Quality of Life Scale (LMSQoL)
Time Frame: 8 mounth
|
The Leeds Multiple Sclerosis Quality of Life Scale (LMSQoL) was developed to assess the quality of life of individuals with MS.
The eight-item form of this scale is directed towards fatigue, loneliness, energy, health concerns, family relationships, appearances, other people's attitudes, and the future.
It is stated that LMSQoL is sensitive and reliable for the studied population and it is fast and easy to use in the clinical setting.
|
8 mounth
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nilüfer ÇETİŞLİ KORKMAZ, Pamukkale University
- Principal Investigator: Zübeyde ERCAN, Firat University
- Principal Investigator: Gökhan ALKAN, Firat University
- Principal Investigator: Murat GÖNEN, Firat University
Publications and helpful links
General Publications
- Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012 Jan 11;481(7382):463-8. doi: 10.1038/nature10777.
- Schmitz-Hubsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schols L, Szymanski S, van de Warrenburg BP, Durr A, Klockgether T, Fancellu R. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006 Jun 13;66(11):1717-20. doi: 10.1212/01.wnl.0000219042.60538.92. Erratum In: Neurology. 2006 Jul 25;67(2):299. Fancellu, Roberto [added].
- Latimer-Cheung AE, Pilutti LA, Hicks AL, Martin Ginis KA, Fenuta AM, MacKibbon KA, Motl RW. Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development. Arch Phys Med Rehabil. 2013 Sep;94(9):1800-1828.e3. doi: 10.1016/j.apmr.2013.04.020. Epub 2013 May 10.
- Motl RW, McAuley E, Snook EM. Physical activity and multiple sclerosis: a meta-analysis. Mult Scler. 2005 Aug;11(4):459-63. doi: 10.1191/1352458505ms1188oa.
- Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G. Exercise therapy for multiple sclerosis. Cochrane Database Syst Rev. 2005 Jan 25;2005(1):CD003980. doi: 10.1002/14651858.CD003980.pub2.
- Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med. 2006 Mar 2;354(9):942-55. doi: 10.1056/NEJMra052130. No abstract available.
- Lassmann H, Bruck W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007 Apr;17(2):210-8. doi: 10.1111/j.1750-3639.2007.00064.x.
- Dalgas U, Stenager E. Progressive resistance therapy is not the best way to rehabilitate deficits due to multiple sclerosis: no. Mult Scler. 2014 Feb;20(2):141-2. doi: 10.1177/1352458513513060. No abstract available.
- Petajan JH, Gappmaier E, White AT, Spencer MK, Mino L, Hicks RW. Impact of aerobic training on fitness and quality of life in multiple sclerosis. Ann Neurol. 1996 Apr;39(4):432-41. doi: 10.1002/ana.410390405.
- Sarova-Pinhas I, Achiron A, Gilad R, Lampl Y. Peripheral neuropathy in multiple sclerosis: a clinical and electrophysiologic study. Acta Neurol Scand. 1995 Apr;91(4):234-8. doi: 10.1111/j.1600-0404.1995.tb06996.x.
- Ayromlou H, Mohammad-Khanli H, Yazdchi-Marandi M, Rikhtegar R, Zarrintan S, Golzari SE, Ghabili K. Electrodiagnostic evaluation of peripheral nervous system changes in patients with multiple sclerosis. Malays J Med Sci. 2013 Jul;20(4):32-8.
- Armutlu K, Karabudak R, Nurlu G. Physiotherapy approaches in the treatment of ataxic multiple sclerosis: a pilot study. Neurorehabil Neural Repair. 2001;15(3):203-11. doi: 10.1177/154596830101500308.
- Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM. Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway. Cell Metab. 2013 Nov 5;18(5):649-59. doi: 10.1016/j.cmet.2013.09.008. Epub 2013 Oct 10.
- Moon HS, Dincer F, Mantzoros CS. Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines. Metabolism. 2013 Aug;62(8):1131-6. doi: 10.1016/j.metabol.2013.04.007. Epub 2013 May 7.
- Novelle MG, Contreras C, Romero-Pico A, Lopez M, Dieguez C. Irisin, two years later. Int J Endocrinol. 2013;2013:746281. doi: 10.1155/2013/746281. Epub 2013 Nov 5.
- Aydin S, Kuloglu T, Aydin S, Eren MN, Celik A, Yilmaz M, Kalayci M, Sahin I, Gungor O, Gurel A, Ogeturk M, Dabak O. Cardiac, skeletal muscle and serum irisin responses to with or without water exercise in young and old male rats: cardiac muscle produces more irisin than skeletal muscle. Peptides. 2014 Feb;52:68-73. doi: 10.1016/j.peptides.2013.11.024. Epub 2013 Dec 15.
- Briken S, Rosenkranz SC, Keminer O, Patra S, Ketels G, Heesen C, Hellweg R, Pless O, Schulz KH, Gold SM. Effects of exercise on Irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis. J Neuroimmunol. 2016 Oct 15;299:53-58. doi: 10.1016/j.jneuroim.2016.08.007. Epub 2016 Aug 5.
- Harvey L, Smith AD, Jones RJP. The effect of weighted leg raises on quadriceps strength, EMG parameters and functional activities in people with multiple sclerosis. 1999;85(3):154-61.
- Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci. 2004 Oct 15;225(1-2):11-8. doi: 10.1016/j.jns.2004.06.009.
- Tsuchiya Y, Mizuno S, Goto K. Irisin response to downhill running exercise in humans. J Exerc Nutrition Biochem. 2018 Jun 30;22(2):12-17. doi: 10.20463/jenb.2018.0011.
- Fischer JS, Rudick RA, Cutter GR, Reingold SC. The Multiple Sclerosis Functional Composite Measure (MSFC): an integrated approach to MS clinical outcome assessment. National MS Society Clinical Outcomes Assessment Task Force. Mult Scler. 1999 Aug;5(4):244-50. doi: 10.1177/135245859900500409.
- Fischer JS, Jak A, Kniker J, Rudick R, Cutter GJNYNMSS. Multiple Sclerosis Functional Composite (MSFC): administration and scoring manual. 2001.
- Armutlu K, Keser I, Korkmaz N, Akbiyik DI, Sumbuloglu V, Guney Z, Karabudak R. Psychometric study of Turkish version of Fatigue Impact Scale in multiple sclerosis patients. J Neurol Sci. 2007 Apr 15;255(1-2):64-8. doi: 10.1016/j.jns.2007.01.073. Epub 2007 Mar 6.
- Polat C, Tulek Z, Kurtuncu M, Eraksoy M. Validity and Reliability of the Turkish Version of the Monitoring My Multiple Sclerosis Scale. Noro Psikiyatr Ars. 2017 Jun;54(2):131-136. doi: 10.5152/npa.2016.12694. Epub 2017 Jan 19.
- Hisli N. Beck Depresyon Olcegi'nin bir Turk ornekleminde gecerlilik ve guvenilirligi. Psikoloji Dergisi 1988; 6:118-122.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- FiratUniversity
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Sclerosis, Relapsing-Remitting
-
BiogenWithdrawnRelapsing-Remitting Multiple Sclerosis | Relapsing Forms of Multiple Sclerosis
-
BiogenAbbVieTerminatedMultiple Sclerosis | Relapsing-Remitting Multiple SclerosisUnited States, Denmark, Italy, United Kingdom, Czechia, Canada, Hungary, Spain, Australia, Israel, Georgia, Serbia, Russian Federation, Ukraine, India, Poland, Brazil, France, Argentina, Germany, Greece, Ireland, Mexico, Moldova, Republic... and more
-
EMD SeronoPfizerCompletedRelapsing-remitting Multiple SclerosisUnited States, United Kingdom, Argentina, Austria, Brazil, France, Germany, Italy, Netherlands, Russian Federation, Spain, Switzerland
-
National Institute of Allergy and Infectious Diseases...Immune Tolerance Network (ITN)CompletedRelapsing-Remitting Multiple SclerosisUnited States
-
BiogenTerminatedRelapsing-Remitting Multiple SclerosisUnited States, Spain, Germany, Australia, Sweden, Czechia, France, Italy, United Kingdom
-
Novartis PharmaceuticalsWithdrawnMultiple Sclerosis (Relapsing Remitting)
-
Genzyme, a Sanofi CompanyTerminatedRelapsing-remitting Multiple SclerosisSweden, Poland, Russian Federation, United States, Canada
-
Novartis PharmaceuticalsCompletedRelapsing-remitting Multiple SclerosisGermany
-
Mitsubishi Tanabe Pharma CorporationCompletedRelapsing-remitting Multiple SclerosisCroatia, Bulgaria, Czech Republic, Italy, Russian Federation, Spain, United Kingdom, Germany, Lithuania, Poland, Belgium, Hungary, Serbia, Finland, Ukraine, Switzerland, Canada, Turkey
-
BiogenCompletedRelapsing-Remitting Multiple SclerosisUnited States
Clinical Trials on Aerobic Exercise
-
Riphah International UniversityCompleted
-
Sultan Abdulhamid Han Training and Research Hospital...RecruitingPhysical InactivityTurkey
-
University of FloridaAmerican Psychological Foundation; Clinical & Translational Science Institute; American Psychological Association (APA)CompletedBrain ConcussionUnited States
-
University of PittsburghNational Heart, Lung, and Blood Institute (NHLBI)TerminatedChildhood ObesityUnited States
-
National Yang Ming UniversityUnknownKnee OsteoarthritisTaiwan
-
Radboud University Medical CenterUniversity Hospital, Bonn; University of Dublin, Trinity College; German Sport... and other collaboratorsCompletedMild Cognitive ImpairmentNetherlands, Ireland, Germany
-
National Defense Medical Center, TaiwanMinistry of Science and Technology, TaiwanRecruitingCardiology | PsychiatryTaiwan
-
Federal University of PelotasMinistry of Health, BrazilUnknownHypertension | Cardiovascular Disease | Chronic Kidney Disease | Chronic Renal DiseaseBrazil
-
University of Kansas Medical CenterRecruiting
-
Norwegian School of Sport SciencesUppsala UniversityRecruitingCardiovascular Diseases | Lymphoma | Cardiotoxicity | Chemotherapeutic Toxicity | Physical ExerciseNorway, Sweden