Ischemic Preconditioning, Exercise Tolerance and Multiple Sclerosis

This project is quantified as a Feasibility study. The design for the study is a double blind randomised control trial. Forty patients with MS above 18 years and who have the ability to walk will be randomised to receive either IPC or sham intervention. Potential candidates will be identified from the MS clinic and Neuro Day Case Unit of the Royal Hallamshire Hospital (RHH) in Sheffield.

All participants will be identified by MS consultants and nurses from MS clinics and from neuroday case unit of Royal Hallamshire Hospital. The patient information sheet will be mailed to the participants deemed suitable for the trial by the treating team. The participants will be given up to two weeks to consider their participation in the trial. Patients wishing to participate will be consented by Dr Siva Nair/Kate Lavender/Dr Ismail, following consent Dr Nair/Kate Lavender/ Dr Ismail will ensure the participants are randomised into the treatment group or the control group using a random number table. The MSc student will act as blinded assessor.

After obtaining consent, the research team will conduct checks against the inclusion criteria to assess whether the participant fulfils the criteria for entry into the study. The participant will then be allocated into one of the two groups using a random number table: Experimental group or the Sham group. Participants will not be told which group they have been randomised to. The researcher will check the participant's blood pressure and heart rate while sitting. Then the researcher will request the participant to walk for six minutes as they normally walk. The researcher will measure the distance covered in 6 minutes and will ask the participant to grade the exertion experienced using Borg's Rating of Perceived Exertion scale. The researcher will again measure the blood pressure and heart rate again.

In the active comparator group The participant will rest in a sitting position for 10 minutes before measuring resting blood pressure. Blood pressure will be measured on the arm. IPC will be administered to the upper arm using cuff inflation pressures of 30mm Hg above the systolic BP using a manual BP. The IPC cycles comprised of three cycles of cuff inflation each lasting 5 min in duration followed by 5-min period of cuff deflation.

Within the sham intervention The participant will rest in a sitting position for 10 min before measuring resting blood pressure. Blood pressure will be measured on the upper arm. Sham intervention will be administered to the right upper limb using a manual BP cuff which will be inflated at a pressure 30mmg Hg below the diastolic blood pressure. The sham cycles comprised of three cycles of cuff inflation each lasting 5 minutes in duration followed by 5-min period of cuff deflation.

The researcher will ask the participant to grade any pain or discomfort experienced during the intervention in a scale of 0 (no pain or discomfort) to 10 (Worst pain or discomfort ever experience).

Ten minutes after the end of the cycle the Researcher will again measure the blood pressure and heart rate. Then the participant will be asked to walk for six minutes with the researcher. The researcher will measure the distance covered in 6 minutes. The researcher will ask the participant to grade the exertion experienced using Rating of Perceived Exertion. The researcher will measure the blood pressure and heart rate again. We anticipate that the patient spend around 2 hours at Royal Hallamshire Hospital for this study.

Inclusion criteria

• Diagnosis of MS as per the McDonald's criteria
• Aged 18 or older
• Sufficient cognitive ability to give informed consent
• Ability to walk for 6 minutes without rest
• Resting Systolic BP of less than 170 mmHg

Exclusion criteria

• Cognitive difficulties in giving consent ad understanding the questionnaire
• Inability to walk
• Other systemic illness affecting exercise tolerance
• Resting systolic BP of 170mmHg or more