Transient and Immediate Motor Effects of Exercise in Progressive Multiple Sclerosis

High-Intensity Interval Training Clinical Trial

— TIME  

Official title:

Transient and Immediate Motor Effects of Exercise in Progressive Multiple Sclerosis: A Pilot Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05562414
• Other study ID #: TIME
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2022
• Est. completion date: April 1, 2023

Study information

• Verified date: October 2022
• Source: Klinik Valens
• Contact: Jens Bansi, PhD
• Phone: +41813031403
• Email: jens.bansi[@]kliniken-valens.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Endurance training is a cornerstone of rehabilitation in Multiple Sclerosis (MS) due to its beneficial effects on multiple MS-related symptoms, such as health-related quality of life, aerobic capacity (VO2peak), functional mobility, gait, depressive symptoms, and fatigue. Persons with progressive phenotypes of MS, namely primary progressive MS (PPMS) and secondary progressive (SPMS), represent a minor proportion of the total MS population, thus having been underrepresented in previous studies. The generalizability of existing evidence may be compromised by differences in symptom expression between MS phenotypes, with a dominance of motor symptoms (i.e., paraspasticity and/or paraparesis) in PPMS and SPMS. Adding up to this, clinical experiences of neurologists and sports scientists reveal that the effects of endurance exercise are characterized by a distinct time course, firstly inducing a minor and transient deterioration of motor symptoms that is followed by motor symptom alleviation beyond baseline level. This phenomenon was mainly related to the performance of High-Intensity Interval training (HIIT), but not to moderate-intensity continuous training (MCT). Therefore, this pilot study aims to systematically investigate the time course of acute motor effects on spasticity, functional mobility, gait, and dexterity in persons with PPMS and SPMS following two different endurance training protocols, that are HIIT and MCT.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: April 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult age (= 18 years)
• definite MS diagnosis according the 2017 revised McDonald criteria
• PPMS/SPMS phenotype according to the 2013 revised Lublin criteria
• Expanded Disability Status Scale (EDSS) score = 6.0
• Informed Consent as documented by signature of participants and PI

Exclusion Criteria:

• severe lower extremity spasticity or severe concomitant disease states (i.e., orthopaedic, cardiovascular, metabolic, psychiatric (e.g., substance abuse), other neurological, other serious medical conditions) impairing the ability to participate
• inability to follow study procedures (e.g., due to language barriers)
• suspected non-compliance
• previous enrolment into the current study
• enrolment of the investigator, his/her family members, employees, and other dependent persons

Related Conditions & MeSH terms

• High-Intensity Interval Training
• Motor Symptoms
• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Sclerosis

Intervention

Behavioral:
• HIIT
Exercise intensity will be regulated and heart rate controlled based on the age-predicted heart rate (HRmax), as calculated by the formula 220 minus age in years. Participants will perform six high-intensity intervals (95% HRmax) at high pedalling rates of 80-100 rounds per minute (rpm) for 60-90 seconds each. Intervals are interspersed by active breaks of unloaded pedalling (20 watts, 60-80rpm) aimed to return to 60% HRmax (approximately 1.5-2 min). The duration of the HIIT bout is approximately 21 minutes.
• MCT
Exercise intensity will be regulated and heart rate controlled based on the age-predicted heart rate (HRmax), as calculated by the formula 220 minus age in years. Participants will continuously train at 60% HRmax and pedal at 60-80 rounds per minute. The duration of the MCT bout is 26 minutes.

Locations

Country	Name	City	State
Switzerland	Klinik Valens, Valens rehabilitation clinic	Valens	Sankt Gallen

Sponsors (1)

Lead Sponsor	Collaborator
Klinik Valens

Country where clinical trial is conducted

Switzerland, 

References & Publications (6)

Bansi J, Koliamitra C, Bloch W, Joisten N, Schenk A, Watson M, Kool J, Langdon D, Dalgas U, Kesselring J, Zimmer P. Persons with secondary progressive and relapsing remitting multiple sclerosis reveal different responses of tryptophan metabolism to acute endurance exercise and training. J Neuroimmunol. 2018 Jan 15;314:101-105. doi: 10.1016/j.jneuroim.2017.12.001. Epub 2017 Dec 6. — View Citation

Ensari I, Motl RW, Pilutti LA. Exercise training improves depressive symptoms in people with multiple sclerosis: results of a meta-analysis. J Psychosom Res. 2014 Jun;76(6):465-71. doi: 10.1016/j.jpsychores.2014.03.014. Epub 2014 Mar 31. — View Citation

Heine M, van de Port I, Rietberg MB, van Wegen EE, Kwakkel G. Exercise therapy for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2015 Sep 11;(9):CD009956. doi: 10.1002/14651858.CD009956.pub2. Review. — View Citation

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. Review. — View Citation

Taul-Madsen L, Connolly L, Dennett R, Freeman J, Dalgas U, Hvid LG. Is Aerobic or Resistance Training the Most Effective Exercise Modality for Improving Lower Extremity Physical Function and Perceived Fatigue in People With Multiple Sclerosis? A Systematic Review and Meta-analysis. Arch Phys Med Rehabil. 2021 Oct;102(10):2032-2048. doi: 10.1016/j.apmr.2021.03.026. Epub 2021 Apr 24. — View Citation

Ward M, Goldman MD. Epidemiology and Pathophysiology of Multiple Sclerosis. Continuum (Minneap Minn). 2022 Aug 1;28(4):988-1005. doi: 10.1212/CON.0000000000001136. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional mobility	Functional mobility is assessed by the Timed-Up-and-Go Test (TUG). For the TUG, participants are asked to get up from a chair, walk a 3 metres distance, perform a 180° turn, return to the chair, and sit down again as fast as possible. Assessment takes place on a single day, before (T0), 5 minutes after (T1), 60 minutes after (T2), 180 minutes after (T3), 300 minutes (T4) after HIIT/MCT cycling bout.	Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout
Secondary	Spasticity (objective)	Spasticity of the hip flexors, knee flexors, foot dorsiflexors and respective extensors will be evaluated using the Modified Ashworth Scale (MAS). The participant is placed on a bench in supine position. The outcome assessor performs a passive stretch on the respective muscle group and scores the muscle tone as normal or increased on a 6-category ordinal scale (0, 1, 1+, 2, 3, 4). Assessment takes place on a single day, before (T0), 5 minutes after (T1), 60 minutes after (T2), 180 minutes after (T3), 300 minutes (T4) after HIIT/MCT cycling bout.	Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout
Secondary	Spasticity (subjective)	Participants rate the extent of perceived spasticity on a Numeric Rating Scale for Spasticity (NRS-S), ranging from 0 ("no spasticity") to 10 ("worst possible spasticity"). Assessment takes place on a single day, before (T0), 5 minutes after (T1), 60 minutes after (T2), 180 minutes after (T3), 300 minutes (T4) after HIIT/MCT cycling bout.	Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout
Secondary	Gait pattern	Spatiotemporal features of the gait pattern analysis are captured by the instrumented treadmill C-Mill for a duration of two minutes. Assessment takes place on a single day, before (T0), 5 minutes after (T1), 60 minutes after (T2), 180 minutes after (T3), 300 minutes (T4) after HIIT/MCT cycling bout.	Change from baseline to directly after, 1-hour after, 3-hours after and 5-hours after the exercise bout
Secondary	Dexterity	Dexterity is assessed by the Virtual Peg Insertion Test (VPIT). The VPIT is a virtual instrumented 3D object manipulation (pick-and-place) task. In seated position, participants are asked to transport virtual pegs into virtual holes as fast as possible. Participants perform four trials with their dominant hand. Spatiotemporal movement trajectories are recorded. Assessment takes place on a single day, before (T0), 5 minutes after (T1), 60 minutes after (T2), 180 minutes after (T3), 300 minutes (T4) after HIIT/MCT cycling bout.	Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout