Clinical trial NCT02264704: Exercise Intensity and Immune Function in Multiple Sclerosis
Official title: Exercise Intensity and Immune Function in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Keywords: MS
Exercise
Training
Multiple sclerosis
Immune response
Neurotrophin
Cytokine
Fatigue
Lead sponsor: University of the West of Scotland
Sponsor class: OTHER
Collaborators: name: National Heatlh Service Ayrshire and Arran
First posted: 2014-10-15
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This study aims to determine the effect of exercise intensity within a 15 week programme in moderately disabled people with multiple sclerosis (MS). Although earlier research has shown that exercise is safe and may improve health related factors such as mobility and fatigue, the intensity at which exercise offers the most benefit has not yet been defined.

Participants will be randomly assigned to one of three groups - high intensity, moderate intensity or usual care. Participants in the exercising groups (high and moderate intensity) will take part in a supervised 15 week cycling exercise programme based in the Douglas Grant Rehabilitation Centre. Those assigned to the usual care (control) group will continue to receive their usual medical care and will not participate in the exercise programme. The acute immune response to exercise will also be measured.

Participants from all three groups will be monitored regularly. Clinical outcomes of the study include immunological markers, exercise capacity, mobility, fatigue, quality of life and cognitive ability. These will be measured by a combination of blood tests, physical assessments and questionnaires.

It is hypothesised that high intensity exercise will cause a favourable, anti-inflammatory response which will be associated with greater improvements in physical and psychological outcomes than both moderate intensity exercise and usual care.

Detailed description: Recruited patients will initially undergo baseline measurements including BMI. Neurotrophin (BDNF and NGF) and cytokine (IFN-Y and IL-4) concentration will be measured from participant serum using commercially available ELISA kits (R\&D systems).

Assessments of cognitive ability, mood, fatigue and quality of life will also be performed using psychometric tests as described in outcomes. Exercise capacity and mobility will be also be measured.

Participants will also undergo a maximal exercise test, recently validated for use in this patient population (Heine et al., 2014). Briefly, rested participants will initially cycle at a power of 25W whilst maintaining a minimum cadence of 60rpm as a 5 minute warm-up. This leads directly into the testing period, during which the power is increased incrementally (15W per minute) until the point of volitional termination or a drop in cadence of 10rpm below the minimum (60 rpm). Peak oxygen consumption (VO2 peak) is used as a measure of cardiorespiratory fitness.

Participants will be randomly assigned to one of three groups - high intensity (HI), moderate intensity (MI) or usual care (UC). Exercising groups will take part in a 15 week programme. All exercise will be performed on a cycle ergometer and will be carried out twice per week for 15 weeks (30 sessions) at the Douglas Grant Rehabilitation Centre, Irvine. In all sessions HI participants will exercise intermittently (30 seconds on 30 seconds off) at 80% of the peak power (based on maximal exercise test) for 15 minutes. MI participants will exercise continuously at 40% peak power for 15 minutes. To ensure exercise intensity remains consistent throughout the programme the workload will progressively increase over time to accommodate any increases in participant fitness levels as measured by %HR. UC participants will not participate in the supervised exercise programme but will continue to receive their usual care.

5 weeks after completion of the exercise programme, a follow-up testing session will occur.

Eligibility criteria: Inclusion Criteria:

* Clinically confirmed MS (according to the revised 2010 McDonald criteria) (Polman et al., 2011)
* Expanded disability status scale (EDSS) 3.0-5.0

Exclusion Criteria:

* Unable to consent due cognitive impairment or mental illness
* Immunomodulatory therapy in past 3 months
* Steroid therapy in the past 6 weeks
* Existence of medical contraindications for exercise i.e. cardiovascular or orthopaedic disease.
* Compounding neurological condition other than MS

Primary outcomes:
measure: Change in serum brain-derived neurotrophic factor (BDNF) level
timeFrame: Chronic - Baseline, week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise
Secondary outcomes:
measure: Change in serum nerve growth factor (NGF) level
timeFrame: Chronic - Baseline, week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise
measure: Change in serum interleukin-4 (IL-4) level
timeFrame: Chronic - Baseline (week 0), week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise
measure: Change in serum interferon gamma (IFN-γ) level
timeFrame: Chronic - Baseline (week 0), week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise
measure: Change in mobility
timeFrame: Baseline, weeks 5, 10, 15 and follow up (week 20)
measure: Change in exercise capacity
timeFrame: Baseline, weeks 5, 10, 15 and follow up (week 20)
measure: Change in fatigue
timeFrame: Baseline, weeks 5, 10, 15 and follow up (week 20)
measure: Change in health-related quality of life
timeFrame: Baseline, weeks 5, 10, 15 and follow up (week 20)
measure: Change in cognitive ability
timeFrame: Baseline, weeks 5, 10, 15 and follow up (week 20)
measure: Number of sessions attended
timeFrame: 15 weeks
measure: Change in cardiorespiratory fitness
timeFrame: Baseline and week 15
measure: Change in mood
timeFrame: Baseline, weeks 5, 10, 15 and follow up (week 20)
Other outcomes:
Locations:
city: Irvine
country: United Kingdom
facility: Douglas Grant Rehabilitation Centre, Ayrshire Central Hospital
state: Ayrshire
Study officials:
affiliation: University of the West of Scotland
name: Ryan Bell, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heine M, Hoogervorst EL, Hacking HG, Verschuren O, Kwakkel G. Validity of maximal exercise testing in people with multiple sclerosis and low to moderate levels of disability. Phys Ther. 2014 Aug;94(8):1168-75. doi: 10.2522/ptj.20130418. Epub 2014 Mar 27.
citation: Collett J, Dawes H, Meaney A, Sackley C, Barker K, Wade D, Izardi H, Bateman J, Duda J, Buckingham E. Exercise for multiple sclerosis: a single-blind randomized trial comparing three exercise intensities. Mult Scler. 2011 May;17(5):594-603. doi: 10.1177/1352458510391836. Epub 2011 Jan 19.