Stroke has an enormous impact on both individual and society. Novel treatments are required to relieve this burden and remote ischaemic conditioning (RIC) is one such approach. RIC refers to applying non-lethal ischaemia to an area distant from an organ you are trying to protect (e.g. the brain). Pre-clinical animal stroke studies have shown RIC to be neuroprotective and help restore functional outcome when compared to control. These outcomes are achieved simply by transiently occluding the blood supply to a limb (e.g. the arm) very soon after the stroke occurs. The mechanisms of protection are unclear but may be due enhancing the body's ability to protect itself from further injury by favorably altering cerebral blood flow or reducing the detrimental effects of oxygen free radicals. Ischaemic conditioning (IC) is an intervention already applied during cardiac surgery to protect the heart from damage and it may be effective after an acute myocardial infarction. The investigators therefore plan to conduct a pilot randomised controlled trial assessing the feasibility of applying RIC (4 cycles of blood pressure cuff inflation for 5 minutes) in patients within 6 hours of ischaemic stroke. The primary outcome is feasibility of RIC. Secondary outcomes include tolerability, safety and clinical efficacy. The results will inform the design of future trials of a potential intervention is that is pragmatic, non-invasive and simple to administer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
1 dose (=4 cycles) of intermittent upper limb ischaemia (1 cycle = 5minutes inflation to 20mmHg above systolic BP, 5 minutes deflation). Dose escalation: (i) Recruits 1-20 receive this cycle once (ii) Recruits 21-40 receive a second dose of 4-cycles one hour after the first. (iii) Recruits 41-60 receive further dosing, twice daily until day 4.
4 cycles of intermittent sham procedure (1 cycle = 5 minutes inflation to 30 mmHg, 5 minutes deflation), matching the dose escalation described in the intervention
Derby Teaching Hospitals Foundation Trust
Derby, Derbyshire, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, Nottinghamshire, United Kingdom
Trial feasibility
Recruitment feasibility (recruitment rate)
Time frame: 90 days
Vascular Event Rate [Safety and Tolerability]
Number of participants with a vascular event (including limb ischaemia, recurrent stroke, myocardial infarction, venous thrombo-embolism)
Time frame: Day 1, Day 4±1, day 90±7
Treatment Related Serious Adverse Event Rates [Safety and Tolerability]
Number of participants with a serious adverse event related to treatment
Time frame: Day 1, Day 4±1, day 90±7
Biomarkers
Plasma S100-beta protein
Time frame: Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1
Biomarkers
Plasma heat-shock proteins
Time frame: Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1
Biomarkers
Plasma cytokines
Time frame: Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1
Impairment
National Institutes of Health Stroke Scale
Time frame: Day 4±1, day 90±7
Dependency
Modified Rankin scale
Time frame: Day 90±7
Disability
Barthel Index
Time frame: Day 90±7
Mood
Zung depression scale
Time frame: Day 90±7
Telephone cognition
Modified Telephone Interview for Cognitive Status (TICS-M)
Time frame: Day 90±7
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