TY - JOUR
T1 - MEsenchymal StEm cells for Multiple Sclerosis (MESEMS)
T2 - a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis
AU - Uccelli, Antonio
AU - Laroni, Alice
AU - Brundin, Lou
AU - Clanet, Michel
AU - Fernandez, Oscar
AU - Nabavi, Seyed Massood
AU - Muraro, Paolo A.
AU - Oliveri, Roberto S.
AU - Radue, Ernst W.
AU - Sellner, Johann
AU - Soelberg Sorensen, Per
AU - Sormani, Maria Pia
AU - Wuerfel, Jens Thomas
AU - Battaglia, Mario A.
AU - Freedman, Mark S.
AU - Bonetti, Bruno
AU - Rush, Carolina
AU - Herrera, Concepción
AU - Ramo Tello, Cristina
AU - Miller, David
AU - Szwajcer, David
AU - Strunk, Dirk
AU - Wall, Donna
AU - Aguera-Morales, Eduardo
AU - Rohde, Eva
AU - Dazzi, Francesco
AU - Comi, Giancarlo
AU - Martino, Gianvito
AU - Izquierdo Ayuso, Guillermo
AU - Rabinovitch, H.
AU - MacLean, Heather
AU - Marriott, James
AU - Racosta, Juan
AU - Arab, Leila
AU - Gimona, Mario
AU - Introna, Martino
AU - Blinkenberg, Morten
AU - Aghdami, Naser
AU - Ali, Rehiana
AU - Vosoughi, Reza
AU - Nicholas, Richard
AU - Marrie, Ruth Ann
AU - Karimi, Shahedeh
PY - 2019/5
Y1 - 2019/5
N2 - Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS. Methods/design: This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects will receive autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. Discussion: Results will provide patients and the scientific community with data on the safety and efficacy of MSC for MS. The innovative approach utilized to obtain funds to support the MESEMS trial could represent a new model to circumvent limitation of funds encountered by academic trials. Trial registration: Andalusia: NCT01745783, registered on Dec 10, 2012. Badalona: NCT02035514 EudraCT, 2010-024081-21. Registered on 2012. Canada: ClinicalTrials.gov, NCT02239393. Registered on September 12, 2014. Copenhagen: EudraCT, 2012-000518-13. Registered on June 21, 2012. Italy: EudraCT, 2011-001295-19, and ClinicalTrials.gov, NCT01854957. Retrospectively registered on May 16, 2013. London: Eudra CT 2012-002357-35, and ClinicalTrials.gov, NCT01606215. Registered on May 25, 2012. Salzburg: EudraCT, 2015-000137-78. Registered on September 15, 2015. Stockholm: ClinicalTrials.gov, NCT01730547. Registered on November 21, 2012. Toulouse: ClinicalTrials.gov, NCT02403947. Registered on March 31, 2015.
AB - Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS. Methods/design: This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects will receive autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. Discussion: Results will provide patients and the scientific community with data on the safety and efficacy of MSC for MS. The innovative approach utilized to obtain funds to support the MESEMS trial could represent a new model to circumvent limitation of funds encountered by academic trials. Trial registration: Andalusia: NCT01745783, registered on Dec 10, 2012. Badalona: NCT02035514 EudraCT, 2010-024081-21. Registered on 2012. Canada: ClinicalTrials.gov, NCT02239393. Registered on September 12, 2014. Copenhagen: EudraCT, 2012-000518-13. Registered on June 21, 2012. Italy: EudraCT, 2011-001295-19, and ClinicalTrials.gov, NCT01854957. Retrospectively registered on May 16, 2013. London: Eudra CT 2012-002357-35, and ClinicalTrials.gov, NCT01606215. Registered on May 25, 2012. Salzburg: EudraCT, 2015-000137-78. Registered on September 15, 2015. Stockholm: ClinicalTrials.gov, NCT01730547. Registered on November 21, 2012. Toulouse: ClinicalTrials.gov, NCT02403947. Registered on March 31, 2015.
KW - Clinical trial
KW - Mesenchymal stem cells
KW - Mesenchymal stromal cells
KW - Multiple sclerosis
U2 - 10.1186/s13063-019-3346-z
DO - 10.1186/s13063-019-3346-z
M3 - Journal article
C2 - 31072380
AN - SCOPUS:85065592919
VL - 20
JO - Trials
JF - Trials
SN - 1745-6215
M1 - 263
ER -