Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke

Laskowitz, D. T. et al. (2023) Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke. Frontiers in Stroke, 2, 1182537. (doi: 10.3389/fstro.2023.1182537)

Abstract

Background and hypothesis: At present, there are no medical interventions proven to improve functional recovery in patients with subacute stroke. We hypothesize that the intraparenchymal administration of CTX0E03, a conditionally immortalized neural stem cell line, linked with a standardized rehabilitation therapy regimen for the upper limb, would improve functional outcomes in patients 6–12 months after an index ischemic stroke. Study design: PISCES III was designed as a multicenter prospective, sham-controlled, outcome-blinded randomized clinical trial. Eligibility required a qualifying ischemic stroke 6–12 months prior to surgical intervention. Patients must be between 35 and 75 years of age and have residual moderate or moderately severe disability (mRS 3 or 4), with the preservation of some residual upper limb movement. All patients received a standardized regimen of home physical therapy following the intervention. Study outcomes: The primary outcome measure is improvement in the modified Rankin Scale (mRS) of disability at 6 months post treatment. Secondary outcomes include assessment of activities of daily living (Barthel Index), functional mobility (Timed Up and Go; Fugl Meyer Assessment), neurological impairment (NIHSS), upper limb function (Chedoke Arm and Hand Inventory), as well as patient related quality of life and global rating scales. Discussion: PISCES III was designed as a randomized trial directly comparing the effects of intraparenchymal injection of a conditional stem cell line vs. sham procedure in patients with subacute stroke. This is one of the first studies of this type to include a standardized minimum rehabilitation protocol. As there are a limited number of studies evaluating invasive stem cell administration in the chronic setting of CNS injury, study design considerations are discussed.

• Item Type: Articles
• Keywords: Stroke therapy, cell based intervention, ischemic stroke (IS), stem cell, stroke outcome measures.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith
• Authors: Laskowitz, D. T., Muir, K. W., Savitz, S. I., Wechsler, L. R., Pilitsis, J. G., Rahimi, S. Y., Beckman, R. L., Holmes, V., Chen, P. R., Juel, L., Koltai, D., and Kolls, B. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Frontiers in Stroke
• Publisher: Frontiers Media
• ISSN: 2813-3056
• ISSN (Online): 2813-3056
• Copyright Holders: Copyright © 2023 Laskowitz, Muir, Savitz, Wechsler, Pilitsis, Rahimi, Beckman, Holmes, Chen, Juel, Koltai and Kolls
• First Published: First published in Frontiers in Stroke 2: 1182537
• Publisher Policy: Reproduced under a Creative Commons License