High-intensity Resistance Training in People With Multiple Sclerosis Experiencing Fatigue

High-intensity Resistance Training in People With Multiple Sclerosis Experiencing Fatigue - Effects on Functioning, Wellbeing and Inflammatory Biological Markers

Fatigue is one of the most frequently reported and disabling impairments in multiple sclerosis (MS) and is associated with activity limitations, participation restrictions and reduced health-related quality of life (HRQL).MS fatigue is thought to be related to the disease itself, where increased levels of inflammatory biological markers (cytokines) are contributing. Resistance training may have an anti-inflammatory effect where a higher intensity is thought to have a more profound effect. Moderate-intensity resistance training is well tolerated in people with MS (PwMS) and can reduce self-reported fatigue. There is, however, a lack of high-quality studies including only fatigued PwMS when evaluating exercise regimes. Furthermore, the optimal dose (i.e. the combination of duration, frequency and intensity) is not known. Our hypothesis is that high-intensity resistance training will have positive effects in fatigued PwMS on functioning (fatigue, mood, activities and participation) and wellbeing/HRQL; and a positive immunomodulatory effect measured by inflammatory biological markers in blood. Further, that high-intensity resistance training twice a week will be superior to once a week

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Fatigue; Cytokines; Resistance Training; Exercise Therapy
• Intervention / Treatment: Other: High-intensity resistance training; Other: Low frequency of high-intensity resistance training

Detailed Description

Multiple sclerosis (MS) is chronic inflammatory neurodegenerative disease. About two-thirds of persons with MS (PwMS) report MS-related fatigue. It is a most disabling impairment and is associated with activity limitations, participation restrictions and reduced health-related quality of life (HRQL). MS fatigue may be related directly to the disease, e.g. inflammation. Resistance training can have direct effects on the MS disease by modulating cytokine levels, where a higher intensity is thought to have a more profound effect. Thus, there are reasons to hypothesise that high-intensity resistance training might reduce fatigue in PwMS. There are, however, no randomized controlled trials (RCTs) on resistance training in PwMS with fatigue. Although the recommendation of resistance training for adults with chronic diseases is twice a week, most primary health-care providers in Sweden only offer supervised training once a week for a limited period, e.g. 8-12 weeks. Thus, our aims are to evaluate the effects of 12 weeks high-intensity resistance training on functioning (fatigue, mood, activities and participation), wellbeing/HRQL and on inflammatory biological markers (e.g. cytokines) in blood. In this two-armed single-blinded RCT, 90 PwMS with fatigue will be recruited and randomly assigned to receive high-intensity resistance training under the supervision from a physiotherapist twice a week (group A) or once a week (group B). Primary outcome is fatigue measured with a patient reported outcome, i.e. the Fatigue Scale for Motor and Cognitive Functions (FSMC), and a change-score of ten points is considered clinically meaningful. Secondary outcomes include measures of mood, participation, self-perceived impact of MS, wellbeing/HRQL and inflammatory biological markers in blood. Data will be collected at baseline and within a week after the last training session of the 12-week intervention. All participants will after the end of intervention be offered a prescription of physical activity (FaR), and have the opportunity for follow-up telephone calls at 3-, 6- and 12 months after the end of the intervention. Assessment of fatigue will also be performed at these follow-up telephone sessions. Fatigue assessments from a natural history cohort (Combat study) will be available for comparisons of natural fluctuations of fatigue.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 11365
    • Academic Specialist Center, , Stockholm Health Services, Region Stockholm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults older than 18 years with the diagnosis MS according to the revised McDonald Criteria, having fatigue (i.e. ≥ 53 FSMC sum score), able to understand and communicate in Swedish, and not practicing high-intensity training within 6 months prior to the trial.

Exclusion Criteria:

• Other conditions or diagnoses judged to potentially interfere with the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; The program consists of high-intensity resistance training for 60 minutes twice a week for group A during 12 weeks at the Karolinska University Hospital under the supervision of a physiotherapist. Participants in group A will have different possible training alternatives every week to ensure availability, and they will train in groups of three to five persons/session.	Other: High-intensity resistance training; The program consists of high-intensity resistance training for 60 minutes twice a week (group A) during 12 weeks
Active Comparator: Group B; The program consists of high-intensity resistance training for 60 minutes once a week for group B during 12 weeks at the Karolinska University Hospital under the supervision of a physiotherapist. Participants in group B will have different possible training alternatives every week to ensure availability, and they will train in groups of three to five persons/session.	Other: Low frequency of high-intensity resistance training; The program consists of high-intensity resistance training for 60 minutes once a week (group B) during 12 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Scale for Motor and Cognitive Functions	Fatigue measured with the FSMC, minimum value 20, maximum value 100, higher scores mean a worse outcome	Directly after the intervention (ie change from assessments at baseline to follow-up after the 12 week intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Severity Scale	Fatigue measured with the FSS, minimum value 1, maximum value 7, higher scores mean a worse outcome	Directly after intervention
Hospital Anxiety and Depression Scale	Mood measured with HADS, Anxiety and depression subscales, minimum value 0, maximum value 21, higher scores mean a worse outcome	Directly after the intervention
Occupational Gaps Questionnaire	Participation in everyday occupations measured with the OGQ, minimum value 0, maximum value 30, higher scores mean a worse outcome	Directly after the intervention
Multiple Sclerosis Impact Scale-29	Health-related quality of life/impact of MS measured with the MS Impact Scale-29, Physical and psychological subscales, minimum value 0, maximum value 100, higher scores mean a worse outcome	Directly after the intervention
Euroqool five dimension five level	Wellbeing/health-related quality of life measured with the EQ-5D-5L, minimum value 0, maximum value 1, higher scores mean a better outcome	Directly after the intervention
Euroqool visual analogue scale	Wellbeing/health-related quality of life measured with the EQ VAS, minimum value 0, maximum value 100, higher scores mean a better outcome	Directly after the intervention
Multiplex proteomic immunoassay and enzyme-linked immunosorbent assay	Analyses of inflammatory biological markers (cytokines) in blood will be analysed, a minimum and maximum value can not be specified, and higher or lower values will have different meaning depending on which biological marker (cytokine)	Directly after the intervention

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Neuro+
• Investigators: Principal Investigator: Marie Kierkegaard, PhD, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2020
• Primary Completion (Actual): June 28, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: September 18, 2020
• First Posted (Actual): September 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue
• Other Study ID Numbers: FOR 4-2358/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results in a publication, after deidentification.
• IPD Sharing Time Frame: Immediately following publication and ending 2 years after publication
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. To achieve the aims in the approved proposal. Proposals should be directed to marie.kierkegaard@ki.se
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No