Transient and Immediate Motor Effects of Exercise in Progressive Multiple Sclerosis

NCT05562414 | Unknown

• 1 other identifier: TIME
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Multiple Sclerosis, Chronic Progressive; Physical Conditioning, Human; Paraparesis; Gait; Dexterity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Spasticity (objective)

  Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout

• Spasticity (subjective)

  Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout

• Gait pattern

  Change from baseline to directly after, 1-hour after, 3-hours after and 5-hours after the exercise bout

• Dexterity

  Change from baseline to directly after, 1-hour after, 3-hours after, and 5-hours after the exercise bout

Study Arms (2)

High-intensity Interval Training (HIIT)

EXPERIMENTAL

Participants will complete one heart-rate-controlled HIIT bout within their 3-week inpatient stay.

Behavioral: HIIT

Moderate Continuous Training (MCT)

ACTIVE COMPARATOR

MCT represents the standard treatment at Valens rehabilitation clinic. Participants will complete one heart-rate-controlled MCT bout within their 3-week inpatient stay.

Behavioral: MCT

Interventions

HIIT BEHAVIORAL

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.

High-intensity Interval Training (HIIT)

MCT BEHAVIORAL

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.

Moderate Continuous Training (MCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Klinik Valens: lead

Study Sites (1)

Klinik Valens, Valens rehabilitation clinic

Valens, Canton of St. Gallen, 7317, Switzerland

RECRUITING

Related Publications (6)

• 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;2015(9):CD009956. doi: 10.1002/14651858.CD009956.pub2.

  PMID: 26358158 BACKGROUND

• 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.

  PMID: 24840141 BACKGROUND

• 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.

  PMID: 23669008 BACKGROUND

• 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.

  PMID: 33901439 BACKGROUND

• 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.

  PMID: 35938654 BACKGROUND

• 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.

  PMID: 29224960 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Motor Activity; Paraparesis

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior; Paresis; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Roman Gonzenbach, MD

  Kliniken Valens

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jens Bansi, PhD

CONTACT

+41813031403; jens.bansi@kliniken-valens.ch

Roman Gonzenbach, MD

CONTACT

+41813031408; Roman.Gonzenbach@kliniken-valens.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding of the principal investigator and research assistant towards group allocation is ensured by a unique subject identification code given to each participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Jens Bansi, Head of Research and Development

Model Details: Single-centre Randomized Controlled Trial (RCT)

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: September 30, 2022
• Study Start: October 1, 2022
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: October 14, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)