AUTHOR=Laskowitz Daniel T. , Muir Keith W. , Savitz Sean I. , Wechsler Lawrence R. , Pilitsis Julie G. , Rahimi Scott Y. , Beckman Richard L. , Holmes Vincent , Chen Peng R. , Juel Laura , Koltai Deborah , Kolls Brad J. 

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

JOURNAL=Frontiers in Stroke

VOLUME=Volume 2 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/stroke/articles/10.3389/fstro.2023.1182537

DOI=10.3389/fstro.2023.1182537

ISSN=2813-3056

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.