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Publications

Journal Article Epublish

PubMed: 42921033 DOI: 10.1002/trc2.70335

A Phase 2a randomized trial of once- versus twice-daily remote ischemic conditioning in vascular cognitive impairment (TRIC-VCI).

Alzheimers Dement (N Y) 12(4):e70335

Authors: Aravind Ganesh, Carlos Camara-Lemarroy, Cheryl R McCreary, Badee Khnaijer, Andrew E Beaudin, Karyn Fischer, Nikita Nukala, Fabrizio Giuliani, Philip A Barber, Sandra E Black, Dale Corbett, Thalia S Field, Richard Frayne, Vladimir C Hachinski, Zahinoor Ismail, Raed A Joundi, Lauren M Mai, Demetrios J Sahlas, Mukul Sharma, Richard H Swartz, Eric E Smith

Affiliations

  • Departments of Clinical Neurosciences, Community Health Sciences and Radiology Cumming School of Medicine University of Calgary Calgary Alberta Canada.
  • The Hotchkiss Brain Institute University of Calgary Calgary Alberta Canada.
  • O'Brien Institute for Public Health University of Calgary Calgary Alberta Canada.
  • Departments of Radiology and Clinical Neurosciences, Cumming School of Medicine University of Calgary Calgary Alberta Canada.
  • Division of Neurology Department of Medicine Neuroscience and Mental Health Institute University of Alberta Edmonton Alberta Canada.
  • Department of Medicine (Neurology), Temerty Faculty of Medicine, Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre University of Toronto Toronto Ontario Canada.
  • Cellular and Molecular Medicine, Canadian Partnership for Stroke Recovery University of Ottawa Ottawa Ontario Canada.
  • Department of Medicine (Neurology), Djavad Mowafaghian Centre for Brain Health, Vancouver Stroke Program University of British Columbia Vancouver British Columbia Canada.
  • Department of Clinical Neurological Sciences Western University London Ontario Canada.
  • Department of Psychiatry, Cumming School of Medicine University of Calgary Calgary Alberta Canada.
  • Department of Medicine (Neurology) Population Health Research Institute McMaster University and Hamilton Health Sciences Hamilton Ontario Canada.

Abstract

INTRODUCTION

Cerebral small vessel disease.(CSVD) is a leading cause of vascular cognitive impairment.(VCI). Remote ischemic conditioning (RIC) is a promising strategy to prevent CSVD progression, but it is unclear what doses of daily RIC are tolerable/adherable for older patients with CSVD-associated VCI.

METHODS

The Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment (TRIC-VCI; ClinicalTrials.gov:NCT04109963) was a prospective, open-label, randomized controlled trial with blinded endpoint assessment. Participants completing 14-day run-in were randomized to once- or twice-daily RIC for 30 days. RIC consisted of four cycles of blood-pressure cuff inflation to 200 mmHg around an arm for 5 minutes followed by 5-minute deflation using automated devices. Inclusion criteria: ages 60 to 85, CSVD evidence on computed tomography/magnetic resonance imaging, Montreal Cognitive Assessment score 13 to 24, and preserved basic activities of daily living. Outcomes were assessed at 30 and 90 days. The primary outcome was adherence (completing ≥ 80% of sessions). Secondary outcomes included percentage of sessions completed, safety, and pain/discomfort ratings. Exploratory outcomes included changes in white matter hyperintensity (WMH) volume, cognitive tests, and blood biomarkers. We explored trial experiences in a focus group with five patient-caregiver dyads.

RESULTS

Twenty-two of 23 patients completed run-in and were randomized. Ten of 11.(90.9%) patients in each RIC-group completed ≥ 80% of sessions; median session completion was 96% (interquartile range [IQR]: 89%-100%) for once-daily and 98% (IQR: 93%-100%) for twice-daily RIC. Pain/discomfort ratings were numerically higher with twice-daily RIC (median rating/10: 4.23, IQR.0.98-4.95 vs. once-daily: 1.63, IQR:1.00-3.36, P = 0.60). No patients developed tissue/neurovascular injury or venous thrombosis. Cognitive tests neither changed nor differed significantly between groups; WMH volumes were stable (90-day change from randomization: -0.21.mL, 95% confidence interval:-0.54 to +0.13). Tumor-necrosis-factor alpha and interleukin-1b declined from baseline to 30 days, persisting at 90 days, in both groups. Focus group participants opined the device was easy to use but desired greater portability, generally favored once-daily RIC, and were open to longer treatment courses in future trials.

DISCUSSION

Patients with CSVD-associated VCI adhered well to once- and twice-daily RIC, with no significant differences in safety or tolerability outcomes. We will incorporate participant feedback into device design and future efficacy trials.

MeSH

Tumor Necrosis Factor-Alpha, Safety, Blood, Focus Groups, Cognitive Dysfunction, Cognition Disorders, Conditioning, Psychological, Ischemic Preconditioning, Cerebral Small Vessel Diseases