Stroke
Conditions
Keywords
Remote ischaemic conditioning
Brief summary
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.
Interventions
PROCEDURERemote ischaemic conditioning
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.
PROCEDURESham
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
Sponsors
University of Nottingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Suspected clinical stroke with 6 hours of onset of neurological symptoms; 2. Age \>18; 3. Written or witnessed oral consent, or relative/consultee advice.
Exclusion criteria
1. Pre-morbid dependency mRS\>3; 2. Dementia; 3. Coma (GCS\< 8); 4. Malignancy or significant co-morbidity thought to limit life expectancy to \<6 months; 5. Blood sugar \< 3.5 mmol/L; 6. Taking part in another clinical trial of an investigational medicinal product (CTIMP); 7. Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trial feasibility | 90 days | Recruitment feasibility (recruitment rate) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Related Serious Adverse Event Rates [Safety and Tolerability] | Day 1, Day 4±1, day 90±7 | Number of participants with a serious adverse event related to treatment |
| Biomarkers | Immediately before RIC/sham at baseline; immediately after RIC/sham on Day 1; day 4±1 | Plasma S100-beta protein |
| Impairment | Day 4±1, day 90±7 | National Institutes of Health Stroke Scale |
| Vascular Event Rate [Safety and Tolerability] | Day 1, Day 4±1, day 90±7 | Number of participants with a vascular event (including limb ischaemia, recurrent stroke, myocardial infarction, venous thrombo-embolism) |
| Disability | Day 90±7 | Barthel Index |
| Mood | Day 90±7 | Zung depression scale |
| Telephone cognition | Day 90±7 | Modified Telephone Interview for Cognitive Status (TICS-M) |
| Dependency | Day 90±7 | Modified Rankin scale |
Countries
United Kingdom
Outcome results
None listed