Remote Ischemic Conditioning With Novel Optical Sensor Feedback Device in Acute Ischemic Stroke

• Hypothesis In patients with ischemic stroke and small vessel disease, Remote Ischemic Conditioning (RIC) delivered by novel device with optical feedback sensor will be safe and feasible.
• Rationale Cerebral small vessel disease (SVD) is highly prevalent in aging societies and also in patients with ischemic stroke.SVD is independently associated with cognitive impairment and incidence of stroke.SVD is characterised by presence of white matter lesions (commonly seen as hyperintensities on magnetic resonance imaging (MRI) or hypodensities on computed tomography, CT), microbleeds, prominent perivascular spaces, lacunar infarcts and intracerebral hemorrhages. Risk of worse outcomes in patients with ischemic stroke as assessed by modified Rankin scale (mRS) >2 is increased by odds ratio (OR) of 1.96 if there is a presence of white-matter hyperintensities (WMH). Furthermore, WMH are also associated with increased risk of recurrent stroke (OR 1.93), cognitive impairment (OR 2.22) and all-cause mortality (OR1.82). Current standard of care focuses on control of vascular risk factors including hypertension, diabetes, dyslipidemia, smoking, physical activity and mental health concerns to reduce the impact of WMH on stroke outcomes. There is no targeted therapy available for reducing the burden of SVD.

RIC involves brief cyclic ischemia (5 minutes, inflation of BP cuff) and reperfusion (5 minutes, deflation of BP cuff) of a distant organ (arm muscles) to protect at-risk (cerebral tissue) organ tissue by increasing ischemia tolerance. In experimental stroke RIC alone or in combination revascularization therapy may have additive effect, improve collateral circulation and reduce the infarct size.Human clinical trial in ischemic stroke have been promising so far. In animal models for vascular contributions to cognitive impairment and dementia (VCID) RIC for 1 month demonstrated improved cerebral blood flow, prevented white matter damage, improved angiogenesis and cognitive outcomes. In a pilot human study RIC for 1 year lead to reduction in WMH.

An important ongoing issue is the fidelity of RIC delivered to the patients. Typically for ischemia to develop in the limb muscles, current standard practice is to increase the pressure in the limb 30-50 mmHg above the systolic blood pressure to maximum of 200 mmHg. However, this may be variable in individual subjects. Pressure in upper limb may be associated with discomfort and consequent reduced compliance.An effective solution would be to identify ideal pressure target for each individual person. Our group is developing a novel RIC device, which will identify precise BP target with optical feedback sensor to deliver optimal ischemia with least possible pressure. This will improve patient experience and improve fidelity of RIC.

Inclusion criteria

• Adult patients with ischemic stroke (anterior and posterior circulation involvement) with or without neurological deficit within 48h of symptom onset
• CT head or MRI Brain evidence of infarct
• CT head or MRI Brain evidence of moderate or severe small vessel disease. We will assess atrophy, leukoaraiosis and old vascular lesions.
• Premorbid functional disability assessed by mRS <2
• National institute of Health Stroke scale <15 at the time of enrollment

Exclusion criteria

• Patient is part of other clinical trial delivering intervention
• Injury to the upper arm or any other musculoskeletal disability/pain precluding from tolerating RIC therapy
• Treatment of ongoing malignancy with expected survival < 6 months
• Presence of hypertensive urgency and emergency
• Presence of hemodynamic instability
• Presence of ongoing systemic infection with antibiotic therapy
• Pregnant and lactating women
• History of dermatological conditions affecting application of tissue perfusion sensor and remote ischemic conditioning pressure cuff