The Influence of HIIT Versus MCT on Cardiorespiratory Fitness in PPMS

NCT05229861 | Unknown

• 1 other identifier: CYPRO
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Endurance training revealed to be an effective means to increase cardiorespiratory fitness in persons with Multiple Sclerosis (MS), considered relevant to health-related quality of life in this population. Moreover, endurance training improves MS-related symptoms, such as reduced walking capacity, fatigue, depression, and cognitive impairment. Owing to these benefits, endurance training has evolved as an integral part of MS rehabilitation, anchored in current treatment guidelines. In recent years, High-Intensity Interval training (HIIT) evolved as a time-efficient and safe alternative to standard care in MS rehabilitation that is Moderate Continuous Training (MCT). Indeed, HIIT has already been proven superior to MCT in improving cardiorespiratory fitness, MS-related symptoms (e.g. cognitive impairment) and, beyond, seems to elicit disease-modifying effects on MS-pathophysiology (i.e. alleviated neuroinflammation and neurodegeneration). However, current evidence is restricted to clinical trials that include samples with mixed MS disease courses, in which persons with primary progressive MS (PPMS) are underrepresented due to comparatively low prevalence rates. Distinct pathophysiological mechanisms and symptom constellations prohibit the generalisation of previous findings to persons with PPMS. In this population, however, evidence-based rehabilitative strategies are urgently needed, as disability progression in PPMS is poorly responsive to pharmacotherapy. This study, aims to validate previous findings on the superior effect of HIIT compared to MCT on improving cardiorespiratory fitness, MS-related symptoms and MS pathophysiology in persons with PPMS, contributing to the development of specific recommendations to maximize the effects of exercise as a potent non-pharmacological treatment adjuvant.

Conditions

Primary Progressive Multiple Sclerosis; Exercise; Cardiorespiratory Fitness

Keywords

Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Exercise; High-intensity Interval Exercise; Rehabilitation; Cardiorespiratory Fitness; Cognition; Mobility limitation; Quality of Life; Fatigue; Depression; Immune signalling; Inflammation; Kynurenine pathway

Outcome Measures

Primary Outcomes (1)

• Cardiorespiratory fitness (peak oxygen consumption, VO2peak)

  Cardiorespiratory fitness will be measured by peak oxygen consumption achieved in the cardiopulmonary exercise test (CPET). Higher values indicate better cardiorespiratory fitness.

  Three weeks (day 0 to day 21)

Secondary Outcomes (10)

• Peak power output (PPO)

  Three weeks (day 0 to day 21)

• Cognitive performance

  Three weeks (day 0 to day 21)

• Cognitive impairment at baseline

  Baseline (day 0)

• Walking capacity

  Three weeks (day 0 to day 21)

• Physical and psychological Impairment

  Three weeks (day 0 to day 21)

Study Arms (2)

High-intensity Interval Training (HIIT)

EXPERIMENTAL

Participants will complete seven HR-controlled HIIT sessions within their 3-week inpatient stay, corresponding to 3 exercise bouts per week.

Behavioral: HIIT

Moderate Continuous Training (MCT)

ACTIVE COMPARATOR

MCT represents the standard treatment at Valens rehabilitation clinic. Participants will complete seven HR-controlled MCT sessions within their 3-week inpatient stay, corresponding to 3 exercise bouts per week.

Behavioral: MCT

Interventions

HIIT BEHAVIORAL

Exercise intensity will be regulated and heart rate controlled based on the achieved maximum heart rate (HRmax) assessed during the initial Cardiopulmonary Exercise Testing. Participants will perform five high-intensity intervals (95% HRpeak) at high pedalling rates of 80-100 rpm for 90 seconds each. Intervals are interspersed by active breaks of unloaded pedalling (20W, 60-70rpm) aimed to return to 60% HRpeak (approximately 1-1.5 min). The duration of a HIIT sessions is approximately 25 minutes.

High-intensity Interval Training (HIIT)

MCT BEHAVIORAL

Exercise intensity will be regulated and heart rate controlled based on the achieved maximum heart rate (HRmax) assessed during the initial Cardiopulmonary Exercise Testing. Participants perform continuous bicycle ergometry at moderate intensity (60% HRpeak) and 60-70 rpm for the duration of 30 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
• disease course: PPMS according to the 2013 revised Lublin criteria
• disease severity: Expanded Disability Status Scale (EDSS) score ≤ 6.0
• Informed Consent as documented by signature of participants and PI

You may not qualify if:

• Persons suffering from 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 their ability to participate.
• Persons regularly performing HIIT (2-3 times per week)
• Inability to follow the procedures of the study due to language problems (i.e., participant not fluent in oral and written German language)
• Changes in disease-modifying drugs (≤ 6 weeks)
• Immunosuppressive therapy (i.e., corticosteroids) (≤ 4 weeks)
• Stem cell treatment (≤ 6 months)
• Pregnant or breast-feeding women
• Intention to become pregnant during the course of the study
• Suspected non-compliance
• Previous enrolment into the current study
• Enrolment of the investigator, his/her family members, employees, and other dependent persons
• occurrence of severe pulmonary or cardiovascular decompensations (i.e., blood pressure (Riva Rocci) \> 240/120, HR ≥ HRmax (220-years of age) (e.g. due to renal failure, hepatic dysfunction, cardiovascular disease)
• abnormalities in electrocardiography (ECG), pulse oximetry, or spirometry during initial CPET

Sponsors & Collaborators

• Klinik Valens: lead
• Technische Universität Dortmund, Germany: collaborator

Study Sites (1)

Klinik Valens, Valens rehabilitation clinic

Valens, Canton of St. Gallen, 7317, Switzerland

RECRUITING

Related Publications (8)

• 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 RESULT

• Zimmer P, Bloch W, Schenk A, Oberste M, Riedel S, Kool J, Langdon D, Dalgas U, Kesselring J, Bansi J. High-intensity interval exercise improves cognitive performance and reduces matrix metalloproteinases-2 serum levels in persons with multiple sclerosis: A randomized controlled trial. Mult Scler. 2018 Oct;24(12):1635-1644. doi: 10.1177/1352458517728342. Epub 2017 Aug 21.

  PMID: 28825348 RESULT

• Joisten N, Proschinger S, Rademacher A, Schenk A, Bloch W, Warnke C, Gonzenbach R, Kool J, Bansi J, Zimmer P. High-intensity interval training reduces neutrophil-to-lymphocyte ratio in persons with multiple sclerosis during inpatient rehabilitation. Mult Scler. 2021 Jun;27(7):1136-1139. doi: 10.1177/1352458520951382. Epub 2020 Sep 3.

  PMID: 32880214 RESULT

• Joisten N, Rademacher A, Warnke C, Proschinger S, Schenk A, Walzik D, Knoop A, Thevis M, Steffen F, Bittner S, Gonzenbach R, Kool J, Bloch W, Bansi J, Zimmer P. Exercise Diminishes Plasma Neurofilament Light Chain and Reroutes the Kynurenine Pathway in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021 Mar 29;8(3):e982. doi: 10.1212/NXI.0000000000000982. Print 2021 May.

  PMID: 33782190 RESULT

• Lea Schlagheck M, Wucherer A, Rademacher A, Joisten N, Proschinger S, Walzik D, Bloch W, Kool J, Gonzenbach R, Bansi J, Zimmer P. VO2peak Response Heterogeneity in Persons with Multiple Sclerosis: To HIIT or Not to HIIT? Int J Sports Med. 2021 Dec;42(14):1319-1328. doi: 10.1055/a-1481-8639. Epub 2021 Jul 1.

  PMID: 34198345 RESULT

• Rademacher A, Joisten N, Proschinger S, Hebchen J, Schlagheck ML, Bloch W, Gonzenbach R, Kool J, Bansi J, Zimmer P. Do baseline cognitive status, participant specific characteristics and EDSS impact changes of cognitive performance following aerobic exercise intervention in multiple sclerosis? Mult Scler Relat Disord. 2021 Jun;51:102905. doi: 10.1016/j.msard.2021.102905. Epub 2021 Mar 18.

  PMID: 33836459 RESULT

• Rademacher A, Joisten N, Proschinger S, Bloch W, Gonzenbach R, Kool J, Langdon D, Bansi J, Zimmer P. Cognitive Impairment Impacts Exercise Effects on Cognition in Multiple Sclerosis. Front Neurol. 2021 Jan 28;11:619500. doi: 10.3389/fneur.2020.619500. eCollection 2020.

  PMID: 33633658 RESULT

• Kupjetz M, Joisten N, Rademacher A, Gonzenbach R, Bansi J, Zimmer P. Cycling in primary progressive multiple sclerosis (CYPRO): study protocol for a randomized controlled superiority trial evaluating the effects of high-intensity interval training in persons with primary progressive multiple sclerosis. BMC Neurol. 2023 Apr 22;23(1):162. doi: 10.1186/s12883-023-03187-6.

  PMID: 37087424 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Motor Activity; Multiple Sclerosis; Mobility Limitation; Fatigue; Depression; Inflammation

Condition Hierarchy (Ancestors)

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; Signs and Symptoms; Behavioral Symptoms

Study Officials

• Roman Gonzenbach, MD

  Klinik Valens

  STUDY DIRECTOR

• Bansi Jens, PhD

  Klinik Valens

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie Kupjetz, cand. PhD

CONTACT

+41813031900.; Marie.Kupjetz@kliniken-valens.ch

Jens Bansi, PhD

CONTACT

+41813031900.; Jens.Bansi@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 & Development

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

Study Record Dates

• First Submitted: January 14, 2022
• First Posted: February 8, 2022
• Study Start: May 10, 2022
• Primary Completion: February 29, 2024
• Study Completion: February 29, 2024
• Last Updated: June 14, 2022

Record last verified: 2022-06

Locations

CH (1)