Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

Introduction Cerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protecti...

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Main Authors: Aravind Ganesh, Zahinoor Ismail, Vladimir Hachinski, Sandra E Black, Eric E Smith, Philip Barber, Dale Corbett, Thalia S Field, Richard Frayne, Lauren M Mai, Cheryl R McCreary, Demetrios Sahlas, Mukul Sharma, Richard H Swartz
Format: Article
Language:English
Published: BMJ Publishing Group 2020-10-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/10/e040466.full
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author Aravind Ganesh
Zahinoor Ismail
Vladimir Hachinski
Sandra E Black
Eric E Smith
Philip Barber
Dale Corbett
Thalia S Field
Richard Frayne
Lauren M Mai
Cheryl R McCreary
Demetrios Sahlas
Mukul Sharma
Richard H Swartz
author_facet Aravind Ganesh
Zahinoor Ismail
Vladimir Hachinski
Sandra E Black
Eric E Smith
Philip Barber
Dale Corbett
Thalia S Field
Richard Frayne
Lauren M Mai
Cheryl R McCreary
Demetrios Sahlas
Mukul Sharma
Richard H Swartz
author_sort Aravind Ganesh
collection DOAJ
description Introduction Cerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysis This prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and dissemination Research Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration number NCT04109963.
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spelling doaj-art-4c41b99e7c6e4a599f1ab09e7e8b9a0c2024-11-16T22:45:07ZengBMJ Publishing GroupBMJ Open2044-60552020-10-01101010.1136/bmjopen-2020-040466Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocolAravind Ganesh0Zahinoor Ismail1Vladimir Hachinski2Sandra E Black3Eric E Smith4Philip Barber5Dale Corbett6Thalia S Field7Richard Frayne8Lauren M Mai9Cheryl R McCreary10Demetrios Sahlas11Mukul Sharma12Richard H Swartz131 Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UKDepartment of Clinical Neurosciences & Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, CanadaDepartment of Clinical Neurological Sciences, Western University, London, Ontario, CanadaDepartment of Medicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaDepartment of Clinical Neurosciences & Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, CanadaDepartments of Clinical Neurosciences, Radiology and Community Health Sciences, University of Calgary, Calgary, Alberta, CanadaDepartment of Cellular & Molecular Medicine, University of Ottawa, Ottawa, Ontario, CanadaDepartment of Medicine (Neurology), University of British Columbia, Vancouver, British Columbia, Canada5 Department of Neuroscience, University of Calgary, Calgary, Alberta, CanadaDepartment of Clinical Neurological Sciences, Western University, London, Ontario, CanadaDepartment of Clinical Neurosciences and Radiology, University of Calgary Faculty of Medicine, Calgary, Alberta, CanadaDepartment of Medicine (Neurology), McMaster University Population Health Research Institute, Hamilton, Ontario, CanadaDepartment of Medicine (Neurology), McMaster University Population Health Research Institute, Hamilton, Ontario, CanadaMedicine (Neurology), Sunnybrook Health Sciences Centre, Toronto, Ontario, CanadaIntroduction Cerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysis This prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and dissemination Research Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration number NCT04109963.https://bmjopen.bmj.com/content/10/10/e040466.full
spellingShingle Aravind Ganesh
Zahinoor Ismail
Vladimir Hachinski
Sandra E Black
Eric E Smith
Philip Barber
Dale Corbett
Thalia S Field
Richard Frayne
Lauren M Mai
Cheryl R McCreary
Demetrios Sahlas
Mukul Sharma
Richard H Swartz
Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol
BMJ Open
title Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol
title_full Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol
title_fullStr Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol
title_full_unstemmed Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol
title_short Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol
title_sort trial of remote ischaemic preconditioning in vascular cognitive impairment tric vci protocol
url https://bmjopen.bmj.com/content/10/10/e040466.full
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