RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.
Timothy J. England,Amanda Hedstrom,Saoirse E. O'Sullivan,Richard Donnelly,David A. Barrett,Sarir Sarmad,Nikola Sprigg,Philip M.W. Bath +7 more
TLDR
RIC after acute stroke is well tolerated and appears safe and feasible, and protective mechanisms may be mediated through HSP27.Abstract:
Background and Purpose— Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke.
Methods— We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures.
Results— Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75–9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group ( P =0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5–5) versus 3 (interquartile range, 2–9.5; P =0.04); RIC augmented plasma HSP27 (heat shock protein 27; P <0.05, repeated 2-way ANOVA) and phosphorylated HSP27 ( P <0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance.
Conclusions— RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted.
Clinical Trial Registration— URL: . Unique identifier: [ISRCTN86672015][1].
[1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN86672015read more
Citations
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Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies.
TL;DR: There is still a substantial need for the development of therapeutic agents for neuroprotection in acute ischemic stroke to protect the brain from damage prior to and during recanalization, extend the therapeutic time window for intervention and further improve functional outcome.
Journal ArticleDOI
Remote Ischemic Conditioning: The Commercial Market: LifeCuff Perspective.
Kirk N. Garratt,Boris Leschinsky +1 more
TL;DR: The market challenges and opportunities linked to the development of a cost-effective, reliable, and clinically effective device for the application of remote ischemic conditioning are presented.
Journal ArticleDOI
Potential Neuroprotective Treatment of Stroke: Targeting Excitotoxicity, Oxidative Stress, and Inflammation
TL;DR: Ischemic conditioning, a phenomenon by which one or more cycles of a short period of sublethal ischemia to an organ or tissue protects against subsequent ischemic events in another organ, may be another potential neuroprotective strategy for the treatment of stroke by targeting key steps in the I/R injury cascade.
Journal ArticleDOI
Preactivation of Notch1 in remote ischemic preconditioning reduces cerebral ischemia-reperfusion injury through crosstalk with the NF-κB pathway
TL;DR: The neuroprotective effect of RIPC against cerebral I/R injury was associated with preactivation of the Notch1 and NF-κB pathways in neurons and significantly improved neurological scores and reduced infarct volume and neuronal apoptosis in rats subjected to I/ R injury.
Journal ArticleDOI
Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection.
TL;DR: An overview of the basic concept and postulated protective mechanisms of RIC is encapsulated, to highlight the main findings from proof-of-concept clinical studies in various clinical scenarios, and to discuss potential obstacles that remain to be conquered.
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Remote Ischemic Perconditioning as an Adjunct Therapy to Thrombolysis in Patients With Acute Ischemic Stroke A Randomized Trial
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