PMID- 32209625 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20210413 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 10 IP - 3 DP - 2020 Mar 24 TI - G-CSF (filgrastim) treatment for amyotrophic lateral sclerosis: protocol for a phase II randomised, double-blind, placebo-controlled, parallel group, multicentre clinical study (STEMALS-II trial). PG - e034049 LID - 10.1136/bmjopen-2019-034049 [doi] LID - e034049 AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurological disorder characterised by a selective degeneration of motor neurons (MNs). Stem cell transplantation is considered as a promising strategy in neurological disorders therapy and the possibility of inducing bone marrow cells (BMCs) to circulate in the peripheral blood is suggested to investigate stem cells migration in degenerated ALS nerve tissues where potentially repair MN damage. Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates haematopoietic progenitor cells, mobilises BMCs into injured brain and it is itself a neurotrophic factor for MN. G-CSF safety in humans has been demonstrated and many observations suggest that it may affect neural cells. Therefore, we decided to use G-CSF to mobilise BMCs into the peripheral circulation in patients with ALS, planning a clinical trial to evaluate the effect of G-CSF administration in ALS patients compared with placebo. METHODS AND ANALYSIS: STEMALS-II is a phase II multicentre, randomised double-blind, placebo-controlled, parallel group clinical trial on G-CSF (filgrastim) and mannitol in ALS patients. Specifically, we investigate safety, tolerability and efficacy of four repeated courses of intravenous G-CSF and mannitol administered in 76 ALS patients in comparison with placebo (indistinguishable glucose solution 5%). We determine increase of G-CSF levels in serum and cerebrospinal fluid as CD34(+) cells and leucocyte count after treatment; reduction in ALS Functional Rating Scale-Revised Score, forced vital capacity, Scale for Testing Muscle Strength Score and quality of life; the adverse events/reactions during the treatment; changes in neuroinflammation biomarkers before and after treatment. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Azienda Ospedaliera Universitaria 'Citta della Salute e della Scienza', Torino, Italy. Results will be presented during scientific symposia or published in scientific journals. TRIAL REGISTRATION NUMBER: Eudract 2014-002228-28. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Salamone, Paolina AU - Salamone P AUID- ORCID: 0000-0001-9038-7816 AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy. FAU - Fuda, Giuseppe AU - Fuda G AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy. FAU - Casale, Federico AU - Casale F AUID- ORCID: 0000-0002-1097-1279 AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy federico.casale@unito.it. FAU - Marrali, Giuseppe AU - Marrali G AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy. FAU - Lunetta, Christian AU - Lunetta C AD - NEuroMuscular Omnicentre (NEMO), Fondazione Serena Onlus, Milan, Italy. FAU - Caponnetto, Claudia AU - Caponnetto C AD - Neurological Clinic, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. FAU - Mazzini, Letizia AU - Mazzini L AD - Department of Neurology, Maggiore della Carita Hospital, University of Piemonte Orientale, Novara, Italy. FAU - La Bella, Vincenzo AU - La Bella V AD - Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Sicilia, Italy. FAU - Mandrioli, Jessica AU - Mandrioli J AD - Department of Neuroscience, Azienda Ospedaliera Universitaria Modena, St. Agostino-Estense Hospital, Modena, Italy. FAU - Simone, Isabella Laura AU - Simone IL AD - Neurology Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Puglia, Italy. FAU - Moglia, Cristina AU - Moglia C AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy. AD - ALS Center, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino, Torino, Piemonte, Italy. FAU - Calvo, Andrea AU - Calvo A AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy. AD - ALS Center, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino, Torino, Piemonte, Italy. FAU - Tarella, Corrado AU - Tarella C AD - Oncohematology Division, IEO European Institute of Oncology, IRCCS, University of Milan, Milano, Lombardia, Italy. FAU - Chio, Adriano AU - Chio A AD - 'Rita Levi Montalcini' Department of Neuroscience, University of Turin, Torino, Piemonte, Italy. AD - ALS Center, Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino, Torino, Piemonte, Italy. CN - STEMALS-II Study Group LA - eng SI - EudraCT/2014-002228-28 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200324 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - PVI5M0M1GW (Filgrastim) SB - IM MH - *Amyotrophic Lateral Sclerosis/drug therapy MH - Clinical Trials, Phase II as Topic MH - Double-Blind Method MH - Filgrastim/*therapeutic use MH - Humans MH - Italy MH - Multicenter Studies as Topic MH - Quality of Life MH - Randomized Controlled Trials as Topic PMC - PMC7202695 OTO - NOTNLM OT - GCS-F OT - amyotrophic lateral sclerosis OT - haematopoietic stem cells OT - randomised clinical trial COIS- Competing interests: None declared. FIR - Bombaci, A IR - Bombaci A FIR - Brunetti, M IR - Brunetti M FIR - Cammarosano, S IR - Cammarosano S FIR - Canosa, A IR - Canosa A FIR - Calvo, C IR - Calvo C FIR - Daviddi, M IR - Daviddi M FIR - De Marco, G IR - De Marco G FIR - Cugnasco, P IR - Cugnasco P FIR - Grassano, M IR - Grassano M FIR - Iazzolino, B IR - Iazzolino B FIR - Ilardi, A IR - Ilardi A FIR - Lauritano, C IR - Lauritano C FIR - Lomartire, A IR - Lomartire A FIR - Manera, U IR - Manera U FIR - Solero, L IR - Solero L FIR - Torrieri R Vasta, M C IR - Torrieri R Vasta MC FIR - Gilestro, M IR - Gilestro M FIR - Muccio P Omede, V E IR - Muccio P Omede VE FIR - Gerardi, F IR - Gerardi F FIR - Cabona, C IR - Cabona C FIR - Novi, G IR - Novi G FIR - Bersano, E IR - Bersano E FIR - De Marchi, F IR - De Marchi F FIR - Spataro, R IR - Spataro R FIR - Scime, R IR - Scime R FIR - Fasano, A IR - Fasano A FIR - Fini, N IR - Fini N FIR - Gessani, A IR - Gessani A FIR - D'Errico, E IR - D'Errico E FIR - Scarafino, A IR - Scarafino A EDAT- 2020/03/27 06:00 MHDA- 2021/04/14 06:00 PMCR- 2020/03/23 CRDT- 2020/03/27 06:00 PHST- 2020/03/27 06:00 [entrez] PHST- 2020/03/27 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/03/23 00:00 [pmc-release] AID - bmjopen-2019-034049 [pii] AID - 10.1136/bmjopen-2019-034049 [doi] PST - epublish SO - BMJ Open. 2020 Mar 24;10(3):e034049. doi: 10.1136/bmjopen-2019-034049.