Exercise Intensity and Immune Function in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Exercise Intensity and Immune Function in Multiple Sclerosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02264704
• Other study ID #: TBD
• Secondary ID: 157624
• Status: Not yet recruiting
• Phase: N/A
• First received: October 8, 2014
• Last updated: October 8, 2014
• Start date: November 2014
• Est. completion date: July 2015

Study information

• Verified date: October 2014
• Source: University of the West of Scotland
• Contact: Paul Mattison, MD
• Phone: 441294323031
• Email: drmattison[@]aaaht.scot.nhs.uk
• Is FDA regulated: No
• Health authority: United Kingdom: National Health ServiceUnited Kingdom: University of the West of Scotland
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 63
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Other:
• High intensity exericse
Participants will exercise at high intensity (70% VO2 peak) intermittently (30 seconds on, 30 seconds off) for 15 minutes, twice weekly for 15 weeks. Workload may increase as the study progresses based on heart rate response.
• Moderate intensity exericse
Participants exercise at moderate intensity (35% VO2 peak) continuously for 15 minutes, twice weekly for 15 weeks. Workload may increase as the study progresses based on heart rate response.

Locations

Country	Name	City	State
United Kingdom	Douglas Grant Rehabilitation Centre, Ayrshire Central Hospital	Irvine	Ayrshire

Sponsors (2)

Lead Sponsor	Collaborator
University of the West of Scotland	National Heatlh Service Ayrshire and Arran

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in serum brain-derived neurotrophic factor (BDNF) level	The level of brain-derived neurotrophic factor in participant serum will be determined by analysing blood samples using commercially available ELISA assays.	Chronic - Baseline, week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise	No
Secondary	Change in serum nerve growth factor (NGF) level	The level of nerve growth factor in participant serum will be determined by analysing blood samples using commercially available ELISA assays.	Chronic - Baseline, week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise	No
Secondary	Change in serum interleukin-4 (IL-4) level	The level of interleukin-4 in participant serum will be determined by analysing blood samples using commercially available ELISA assays.	Chronic - Baseline (week 0), week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise	No
Secondary	Change in serum interferon gamma (IFN-?) level	The level of interferon gamma in participant serum will be determined by analysing blood samples using commercially available ELISA assays.	Chronic - Baseline (week 0), week 7, week 15 and follow-up (week 20). Acute - 15 mins, 30 mins and 1 hour post-exercise	No
Secondary	Change in mobility	Participant mobility and balance will be assessed by the timed up and go test (TUG). Individuals safely rise from a standard armchair, walk a distance of 3 metres, turn around and return to a seated position. Usual walking aids may be used however personal assistance is not permitted.	Baseline, weeks 5, 10, 15 and follow up (week 20)	No
Secondary	Change in exercise capacity	Exercise capacity will be assessed by the six minute walk test (6MWT). Participants walk continuously, turning at a defined distance, until six minutes have passed. Total distance travelled is the measured outcome.	Baseline, weeks 5, 10, 15 and follow up (week 20)	No
Secondary	Change in fatigue	Self-reported fatigue will be assessed by the 21 item modified fatigue impact scale (MFIS) which has been previously validated for use in this patient population.	Baseline, weeks 5, 10, 15 and follow up (week 20)	No
Secondary	Change in health-related quality of life	Health-related quality of life will be assessed by the 29 item multiple sclerosis impact scale questionnaire (MSIS-29). MSIS-29 analyses both mental and physical aspects of quality of life.	Baseline, weeks 5, 10, 15 and follow up (week 20)	No
Secondary	Change in cognitive ability	The brief international cognitive assessment for multiple sclerosis (BICAMS) is a short test battery which assesses information processing speed, visual memory and verbal learning ability.	Baseline, weeks 5, 10, 15 and follow up (week 20)	No
Secondary	Number of sessions attended	Adherence will be measured by number of exercise sessions attended across the 15 week intervention (30 sessions).	15 weeks	No
Secondary	Change in cardiorespiratory fitness	Peak oxygen consumption (VO2 peak) will be measured via a maximal exercise test tailored for this patient population (Heine et al., 2014).	Baseline and week 15	No
Secondary	Change in mood	Mood will be assessed by the hospital anxiety and depression scale (HADS). HADS is a 14 item questionnaire designed to analyse self-reported indicators of anxiety and depression.	Baseline, weeks 5, 10, 15 and follow up (week 20)	No