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A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia
BACKGROUND: Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial pote...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688296/ https://www.ncbi.nlm.nih.gov/pubmed/23758736 http://dx.doi.org/10.1186/1479-5876-11-143 |
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author | Gupta, Pawan K Chullikana, Anoop Parakh, Rajiv Desai, Sanjay Das, Anjan Gottipamula, Sanjay Krishnamurthy, Sagar Anthony, Naveen Pherwani, Arun Majumdar, Anish S |
author_facet | Gupta, Pawan K Chullikana, Anoop Parakh, Rajiv Desai, Sanjay Das, Anjan Gottipamula, Sanjay Krishnamurthy, Sagar Anthony, Naveen Pherwani, Arun Majumdar, Anish S |
author_sort | Gupta, Pawan K |
collection | PubMed |
description | BACKGROUND: Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. METHODS: Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. RESULTS: Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. CONCLUSION: BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. TRIAL REGISTRATION: NIH website (http://www.clinicaltrials.gov/ct2/show/NCT00883870) |
format | Online Article Text |
id | pubmed-3688296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36882962013-06-21 A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia Gupta, Pawan K Chullikana, Anoop Parakh, Rajiv Desai, Sanjay Das, Anjan Gottipamula, Sanjay Krishnamurthy, Sagar Anthony, Naveen Pherwani, Arun Majumdar, Anish S J Transl Med Research BACKGROUND: Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI. METHODS: Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb. RESULTS: Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells. CONCLUSION: BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies. TRIAL REGISTRATION: NIH website (http://www.clinicaltrials.gov/ct2/show/NCT00883870) BioMed Central 2013-06-10 /pmc/articles/PMC3688296/ /pubmed/23758736 http://dx.doi.org/10.1186/1479-5876-11-143 Text en Copyright © 2013 Gupta et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Gupta, Pawan K Chullikana, Anoop Parakh, Rajiv Desai, Sanjay Das, Anjan Gottipamula, Sanjay Krishnamurthy, Sagar Anthony, Naveen Pherwani, Arun Majumdar, Anish S A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
title | A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
title_full | A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
title_fullStr | A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
title_full_unstemmed | A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
title_short | A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
title_sort | double blind randomized placebo controlled phase i/ii study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688296/ https://www.ncbi.nlm.nih.gov/pubmed/23758736 http://dx.doi.org/10.1186/1479-5876-11-143 |
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