Remote Ischaemic Conditioning for Fatigue After Stroke

Safety of a 6-week RIC intervention will be assessed by measuring the Number of Participants With Adverse Events That Are Related to Treatment.

Compliance to RIC will be defined as achievement of 80% of intended RIC cycles. This will be assessed by a mobile compliance application.

Reported grade of discomfort associated with RIC will be measured on a likert scale of 0-5, 0 being no discomfort 5 being great discomfort. Acceptance of RIC will be defined as less than 1/3 of participants reporting moderate or greater discomfort (3-4 on scale) and will be supported by qualitative interviews and diary recordings.

Study recruitment will be deemed feasible if four participants are recruited within the first 2 months.

Study assessments will be deemed feasible if >80% of assessments are completed.

Number of participants with changes to full blood count between baseline and after 6 week intervention period, leading to them lying outside the 'normal' range according to Sheffield Teaching Hospitals reference ranges. Any concerns or significant abnormalities will be referred to the principle investigator for appropriate action to ensure the safety of the participant.

Number of participants with changes to U&E concentration between baseline and after 6 week intervention period, leading to them lying outside the 'normal' range according to Sheffield Teaching Hospitals reference ranges. Any concerns or significant abnormalities will be referred to the principle investigator for appropriate action to ensure the safety of the participant.

Number of participants with changes to liver function as measured by the liver function test (LFT) between baseline and after 6 week intervention period, leading to them lying outside the 'normal' range according to Sheffield Teaching Hospitals reference ranges. Any concerns or significant abnormalities will be referred to the principle investigator for appropriate action to ensure the safety of the participant.

The inflammatory marker (CRP) will be measured at baseline and after 6 week intervention period to assess if there has been a change in concentration between baseline and after the intervention.

ESR will be measured at baseline and after 6 week intervention period as a measure of inflammation.

Measured at baseline and after 6 week intervention period.

Energy expenditure (kCal) will be measured using ACTiheart by CamnTech throughout the intervention period and changes from the baseline reviewed at the end of the 6 week intervention.

The Global Physical Activity Questionnaire (GPAQ) measures physical activity levels from 3 domains: Activity at work, Travel to and from places, Recreational activities, as well as sedentary behaviour, in 16 questions, P1-P16. To analyse GPAQ data, metabolic equivalents (METs) are used to express the intensity of physical activities. MET is the ratio of a person's working relative to resting metabolic rate. Higher MET values indicate more intense activity. MET values are applied to time variables according to the intensity of the activity, 4 METS for time spent in moderate activities and 8 METS for vigorous activities. Mean/median time of physical activity on average per day is calculated by summing MET scores for all domains to calculate average activity per week, and dividing this score by 7 (p1t3+p4t6+p7t9+p10t12+p13t15)/7). The questionnaire will be completed at baseline and after 6 week intervention.

The six minute walk test (6 MWT) is an exercise test that entails measurement of distance walked over a span of 6 minutes. Researcher will record the total distance walked, heart rate, blood pressure and Rating of Perceived Exertion (RPE). This will be done at baseline and after 6 week intervention period.

At baseline and after 6 week intervention period.

Measured with multidimensional fatigue inventory (MFI), a self report measure of fatigue. Participants indicate level of agreement with numerous statements associated with fatigue on a scale of 1-7, 1 being strongly disagree 7 being strongly agree. This is measured at baseline and after 6 week intervention period.

Disability after stroke will be measured using modified rankin score (MRS), a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Symptoms are rated on a scale of 0 - 6, with 0 being 'no disability', rising in symptom severity to 6 being 'dead'. MRS will be taken at baseline and after 6 week intervention period.

Measured using Barthel Index (BI), an ordinal scale used to measure performance in 10 items (activities of daily living (ADL)). Items are rated on a scale from 0 - 15 in increments of 5, with 0 being least independent and 15 being most independent. Scores for all items are added up to give a total score out of 100, with higher scores equating to more independence. This is taken at baseline and after 6 week intervention period.

Depression will be measured using Patient Health Questionnaire (PHQ9). The patient indicates how many times over the last two weeks have they been bothered by a series of 9 issues. The scale ranges from 0/not at all to 3/ nearly every day. Scores from each item are added to produce a final score out of 27, with scores 0-4 indicating no depression, 5-9 mild depression, 10-14 moderate depression, 15-19 moderately severe depression and 20-27 severe depression. This is taken at baseline and after 6 week intervention period.

Anxiety will be measured using the Generalised anxiety disorder assessment (GAD7). The patient indicates how many times over the last two weeks have they been bothered by a series of 7 issues. The scale ranges from 0/not at all to 3/ nearly every day. Scores from each item are added to produce a final score out of 21, Scores represent: 0-5 mild anxiety, 6-10 moderate anxiety, 11-15 moderately severe anxiety and 15-21 severe anxiety.This is taken at baseline and after 6 week intervention period.

Cognitive dysfunction will be measured using Montreal Cognitive Assessment (MOCA). This is a test with 8 domains, scores on each domain are added to produce a final score out of 30, with 26-30 equating to normal cognitive function. This will be completed at baseline and after 6 week intervention period.

Health Related Quality of Life will be measured by the EQ5D questionnaire at baseline and after 6 week intervention. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.

For a subset of patients who consent to having the MRI perfusion and spectroscopy studies as well as the blood analysis of biomarkers, blood samples will be analysed for GLP-1 levels at baseline and after 6 week intervention.

For a subset of patients who consent to having the MRI perfusion and spectroscopy studies as well as the blood analysis of biomarkers, blood samples will be analysed for heat shock protein levels at baseline and after 6 week intervention.

For a subset of patients who consent to having the MRI perfusion and spectroscopy studies as well as the blood analysis of biomarkers, changes in cerebral perfusion between baseline and after 6-week intervention period will be analysed.

For a subset of patients who consent to having the MRI perfusion and spectroscopy studies as well as the blood analysis of biomarkers, changes in levels of tissue metabolite N-acetyl aspartate (that may indicate loss or damage to neuronal tissue) between baseline and after 6-week intervention period will be analysed.

For a subset of patients who consent to having the MRI perfusion and spectroscopy studies as well as the blood analysis of biomarkers, changes in levels of tissue metabolite creatine (that may indicate cell death through ischaemia) between baseline and after 6-week intervention period will be analysed.

For a subset of patients who consent to having the MRI perfusion and spectroscopy studies as well as the blood analysis of biomarkers, changes in levels of tissue metabolite lactate between baseline and after 6-week intervention period will be analysed.