Clinical trial NCT04562376: High-intensity Resistance Training in People With Multiple Sclerosis Experiencing Fatigue
Official title: High-intensity Resistance Training in People With Multiple Sclerosis Experiencing Fatigue - Effects on Functioning, Wellbeing and Inflammatory Biological Markers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Fatigue
Exercise Therapy
Resistance Training
Cytokines
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Neuro+
First posted: 2020-09-24
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two-armed single-blinded randomized controlled trial of high-intensity resistance training in PwMS with fatigue where one group receive training twice a week (group A) and the other group once a week (group B). The randomization procedure will be performed after baseline assessments and will be concealed and based on computer-generated block randomization with block sizes of ten. No stratification will be used. Implementation of the random allocation will be done by means of sequentially numbered sealed opaque envelops.
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fatigue Scale for Motor and Cognitive Functions
timeFrame: Directly after the intervention (ie change from assessments at baseline to follow-up after the 12 week intervention)
Secondary outcomes:
measure: Fatigue Severity Scale
timeFrame: Directly after intervention
measure: Hospital Anxiety and Depression Scale
timeFrame: Directly after the intervention
measure: Occupational Gaps Questionnaire
timeFrame: Directly after the intervention
measure: Multiple Sclerosis Impact Scale-29
timeFrame: Directly after the intervention
measure: Euroqool five dimension five level
timeFrame: Directly after the intervention
measure: Euroqool visual analogue scale
timeFrame: Directly after the intervention
measure: Multiplex proteomic immunoassay and enzyme-linked immunosorbent assay
timeFrame: Directly after the intervention
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Academic Specialist Center, , Stockholm Health Services, Region Stockholm
Study officials:
affiliation: Karolinska Institutet
name: Marie Kierkegaard, PhD
role: PRINCIPAL_INVESTIGATOR
References: