1. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis
- Author
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Uccelli, Antonio, Laroni, Alice, Brundin, Lou, Clanet, Michel, Fernandez, Oscar, Nabavi, Seyed Massood, Muraro, Paolo A., Oliveri, Roberto S., Radue, Ernst W., Sellner, Johann, Soelberg Sorensen, Per, Sormani, Maria Pia, Wuerfel, Jens Thomas, Battaglia, Mario A., Freedman, Mark S., Bonetti, Bruno, Rush, Carolina, Herrera, Concepción, Ramo Tello, Cristina, Miller, David, Szwajcer, David, Strunk, Dirk, Wall, Donna, Aguera-Morales, Eduardo, Rohde, Eva, Dazzi, Francesco, Comi, Giancarlo, Martino, Gianvito, Izquierdo Ayuso, Guillermo, Rabinovitch, H., MacLean, Heather, Marriott, James, Racosta, Juan, Arab, Leila, Gimona, Mario, Introna, Martino, Blinkenberg, Morten, Aghdami, Naser, Ali, Rehiana, Vosoughi, Reza, Nicholas, Richard, Marrie, Ruth Ann, Karimi, Shahedeh, The UK Stem Cell Foundation, Multiple Sclerosis Society, MESEMS study group, [Uccelli,A, Laroni,A] Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genoa, Italy. [Uccelli,A, Laroni,A] IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [Brundin,L] Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden [Clanet,M] CHU Toulouse, Université Paul Sabatier, Toulouse, France. [Fernandez,O] Instituto de Investigación Biomédica de Málaga (IBIMA), Regional University Hospital of Malaga, Malaga, Spain. [Nabavi,SM] Department of Brain and Cognitive Sciences, Royan Institute for Stem Cell Biology and Technology, Royan, Iran. [Nabavi,SM] ACCR, Iran and Regenerative Biomedicine Center, MS, Neurology Clinic and Research Unit, Tehran, Iran. [Muraro,PA] Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK. [Oliveri,RS] Cell Therapy Unit, Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. [Radue,EW, Wuerfel,JT] Medical Image Analysis Centre Basel (MIAC AG), Basel, Switzerland. [Sellner,J] Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, Salzburg, Austria. [Soelberg Sorensen,P] Danish MS Center Department of Neurology, University of Copenhagen and Rigshospitalet, Copenhagen, Denmark. [Sormani,MP] Department of Health Sciences, University of Genoa, Genoa, Italy. [Wuerfel,JT] Department of Biomedical Engineering, University Basel, Basel, Switzerland. [Battaglia,MA] Italian Multiple Sclerosis Foundation, Genoa, Italy. [Battaglia,MA] Department of Life Sciences, University of Siena, Siena, Italy. [Freedman,MS] Department of Medicine (Neurology), University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., The MESEMS network received a grant from Fondazione Italiana Sclerosi Multipla (FISM, sponsor of the Italian Clinical Trial, of the CRO activities and of part of centralized MRI activities), European Committee for Multiple Sclerosis (ECTRIMS), Multiple Sclerosis International Foundation (MSIF) for centralized activities. Individual trials participating in the MESEMS network are funded by: FISM (Italy), The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark), Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria (Austria), ARSEP Foundation, AFM (France). The UK trial (London) is supported by a Collaborative Grant from the UK MS Society [938/10], by the NIHR Biomedical Research Centre funding scheme to Imperial College and by the NIHR Imperial Clinical Research Facility., Uccelli, A., Laroni, A., Brundin, L., Clanet, M., Fernandez, O., Nabavi, S. M., Muraro, P. A., Oliveri, R. S., Radue, E. W., Sellner, J., Soelberg Sorensen, P., Sormani, M. P., Wuerfel, J. T., Battaglia, M. A., Freedman, M. S., Bonetti, B., Rush, C., Herrera, C., Ramo Tello, C., Miller, D., Szwajcer, D., Strunk, D., Wall, D., Aguera-Morales, E., Rohde, E., Dazzi, F., Comi, G., Martino, G., Izquierdo Ayuso, G., Rabinovitch, H., Maclean, H., Marriott, J., Racosta, J., Arab, L., Gimona, M., Introna, M., Blinkenberg, M., Aghdami, N., Ali, R., Vosoughi, R., Nicholas, R., Marrie, R. A., and Karimi, S.
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Male ,Time Factors ,Phenomena and Processes::Physical Phenomena::Time::Time Factors [Medical Subject Headings] ,Mesenchymal stromal cells ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings] ,Medicine (miscellaneous) ,Phases of clinical research ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Transplantation, Autologous [Medical Subject Headings] ,NEUROLOGICAL DISEASES ,Research & Experimental Medicine ,Geographical Locations::Geographic Locations::Europe::Europe, Eastern [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Clinical Trials, Phase I as Topic [Medical Subject Headings] ,Study Protocol ,Disability Evaluation ,Clinical trial, Mesenchymal stem cells, Mesenchymal stromal cells, Multiple sclerosis ,0302 clinical medicine ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings] ,Multicenter Studies as Topic ,Pharmacology (medical) ,030212 general & internal medicine ,1102 Cardiorespiratory Medicine and Haematology ,Randomized Controlled Trials as Topic ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic [Medical Subject Headings] ,Cross over ,lcsh:R5-920 ,Cross-Over Studies ,Clinical Trials, Phase I as Topic ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Clinical Trials, Phase II as Topic [Medical Subject Headings] ,Middle Aged ,Magnetic Resonance Imaging ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Disability Evaluation [Medical Subject Headings] ,Clinical trial ,Europe ,Treatment Outcome ,Medicine, Research & Experimental ,EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS ,Female ,lcsh:Medicine (General) ,Autologous ,Life Sciences & Biomedicine ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,Células madre mesenquimatosas ,Check Tags::Male [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell Transplantation [Medical Subject Headings] ,Phase I as Topic ,Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [Medical Subject Headings] ,Mesenchymal Stem Cell Transplantation ,Placebo ,Transplantation, Autologous ,Persons::Persons::Age Groups::Adolescent [Medical Subject Headings] ,Double blind ,Young Adult ,03 medical and health sciences ,Clinical Trials, Phase II as Topic ,Double-Blind Method ,General & Internal Medicine ,Internal medicine ,Ensayo clínico ,medicine ,Humans ,Clinical Trials ,Persons::Persons::Age Groups::Adult [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Science & Technology ,TRANSPLANTATION ,business.industry ,Multiple sclerosis ,Phase II as Topic ,Mesenchymal stem cell ,MESEMS study group ,Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,1103 Clinical Sciences ,Recovery of Function ,medicine.disease ,Phenomena and Processes::Biological Phenomena::Recovery of Function [Medical Subject Headings] ,Transplantation ,Check Tags::Female [Medical Subject Headings] ,Cardiovascular System & Hematology ,Esclerosis múltiple ,Mesenchymal stem cells ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Cross-Over Studies [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Double-Blind Method [Medical Subject Headings] ,business ,030217 neurology & neurosurgery - Abstract
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. 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. 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. 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.
- Published
- 2019