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Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, pla...

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Autores principales: de Celis-Ruiz, Elena, Fuentes, Blanca, Alonso de Leciñana, María, Gutiérrez-Fernández, María, Borobia, Alberto M., Gutiérrez-Zúñiga, Raquel, Ruiz-Ares, Gerardo, Otero-Ortega, Laura, Laso-García, Fernando, Gómez-de Frutos, Mari Carmen, Díez-Tejedor, Exuperio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943307/
https://www.ncbi.nlm.nih.gov/pubmed/35301883
http://dx.doi.org/10.1177/09636897221083863
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author de Celis-Ruiz, Elena
Fuentes, Blanca
Alonso de Leciñana, María
Gutiérrez-Fernández, María
Borobia, Alberto M.
Gutiérrez-Zúñiga, Raquel
Ruiz-Ares, Gerardo
Otero-Ortega, Laura
Laso-García, Fernando
Gómez-de Frutos, Mari Carmen
Díez-Tejedor, Exuperio
author_facet de Celis-Ruiz, Elena
Fuentes, Blanca
Alonso de Leciñana, María
Gutiérrez-Fernández, María
Borobia, Alberto M.
Gutiérrez-Zúñiga, Raquel
Ruiz-Ares, Gerardo
Otero-Ortega, Laura
Laso-García, Fernando
Gómez-de Frutos, Mari Carmen
Díez-Tejedor, Exuperio
author_sort de Celis-Ruiz, Elena
collection PubMed
description Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8–20) were randomized (1:1) to receive intravenous adipose tissue–derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3–5.5] vs 7 [0–8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up.
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spelling pubmed-89433072022-03-25 Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial de Celis-Ruiz, Elena Fuentes, Blanca Alonso de Leciñana, María Gutiérrez-Fernández, María Borobia, Alberto M. Gutiérrez-Zúñiga, Raquel Ruiz-Ares, Gerardo Otero-Ortega, Laura Laso-García, Fernando Gómez-de Frutos, Mari Carmen Díez-Tejedor, Exuperio Cell Transplant Original Article Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8–20) were randomized (1:1) to receive intravenous adipose tissue–derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3–5.5] vs 7 [0–8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up. SAGE Publications 2022-03-18 /pmc/articles/PMC8943307/ /pubmed/35301883 http://dx.doi.org/10.1177/09636897221083863 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
de Celis-Ruiz, Elena
Fuentes, Blanca
Alonso de Leciñana, María
Gutiérrez-Fernández, María
Borobia, Alberto M.
Gutiérrez-Zúñiga, Raquel
Ruiz-Ares, Gerardo
Otero-Ortega, Laura
Laso-García, Fernando
Gómez-de Frutos, Mari Carmen
Díez-Tejedor, Exuperio
Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial
title Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial
title_full Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial
title_fullStr Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial
title_full_unstemmed Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial
title_short Final Results of Allogeneic Adipose Tissue–Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial
title_sort final results of allogeneic adipose tissue–derived mesenchymal stem cells in acute ischemic stroke (amascis): a phase ii, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943307/
https://www.ncbi.nlm.nih.gov/pubmed/35301883
http://dx.doi.org/10.1177/09636897221083863
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