Clinical trial NCT05229861: The Influence of HIIT Versus MCT on Cardiorespiratory Fitness in PPMS
Official title: The Influence of High-Intensity Interval Training Compared to Moderate Continuous Training on Cardiorespiratory Fitness, Symptom Improvement, and Disease-specific Biomarkers in Primary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: Klinik Valens
Sponsor class: OTHER
Collaborators: name: Technische Universität Dortmund, Germany
First posted: 2022-02-08
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-centre Randomized Controlled Trial (RCT)
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Cardiorespiratory fitness (peak oxygen consumption, VO2peak)
timeFrame: Three weeks (day 0 to day 21)
Secondary outcomes:
measure: Peak power output (PPO)
timeFrame: Three weeks (day 0 to day 21)
measure: Cognitive performance
timeFrame: Three weeks (day 0 to day 21)
measure: Cognitive impairment at baseline
timeFrame: Baseline (day 0)
measure: Walking capacity
timeFrame: Three weeks (day 0 to day 21)
measure: Physical and psychological Impairment
timeFrame: Three weeks (day 0 to day 21)
measure: Fatigue
timeFrame: Three weeks (day 0 to day 21)
measure: Anxiety and depressive symptoms
timeFrame: Three weeks (day 0 to day 21)
measure: Kynurenine pathway (KP) metabolites
timeFrame: Three weeks (day 0 to day 21)
measure: Immune status (blood cells)
timeFrame: Time Frame: Three weeks (day 0 to day 21)
measure: Immune status (pro-inflammatory cytokines)
timeFrame: Time Frame: Three weeks (day 0 to day 21)
Other outcomes:
Locations:
city: Valens
country: Switzerland
facility: Klinik Valens, Valens rehabilitation clinic
state: Sankt Gallen
Study officials:
affiliation: Klinik Valens
name: Roman Gonzenbach, MD
role: STUDY_DIRECTOR
affiliation: Klinik Valens
name: Bansi Jens, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.