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)

P. Salamone, G. Fuda, F. Casale, G. Marrali, C. Lunetta, C. Caponnetto, L. Mazzini, V. La Bella, J. Mandrioli, I.L. Simone, C. Moglia, A. Calvo, C. Tarella, A. Chio

Research output: Contribution to journalArticlepeer-review

Abstract

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 Città 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. © 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.
Original languageEnglish
JournalBMJ Open
Volume10
Issue number3
DOIs
Publication statusPublished - 2020

Keywords

  • amyotrophic lateral sclerosis
  • GCS-F
  • haematopoietic stem cells
  • randomised clinical trial
  • alkaline phosphatase
  • aspartate aminotransferase
  • biological marker
  • CD34 antigen
  • chemokine
  • cytokine
  • filgrastim
  • glucose
  • granulocyte colony stimulating factor
  • lactate dehydrogenase
  • mannitol
  • paracetamol
  • reduced nicotinamide adenine dinucleotide phosphate oxidase 2
  • acute febrile neutrophilic dermatosis
  • adult
  • aged
  • allergic reaction
  • ALS Functional Rating Scale Revised Score
  • Article
  • bone marrow cell
  • capillary leak syndrome
  • clinical evaluation
  • controlled study
  • disease exacerbation
  • double blind procedure
  • drug effect
  • drug efficacy
  • drug safety
  • drug tolerability
  • enzyme activity
  • follow up
  • forced vital capacity
  • headache
  • human
  • human tissue
  • hypersensitivity
  • hyperuricemia
  • leukocyte count
  • leukocytosis
  • major clinical study
  • metabolic disorder
  • multicenter study
  • muscle strength
  • musculoskeletal pain
  • nervous system inflammation
  • nutritional disorder
  • peripheral circulation
  • pharmacovigilance
  • phase 2 clinical trial
  • protein blood level
  • protein cerebrospinal fluid level
  • quality of life
  • randomized controlled trial
  • rating scale
  • rheumatoid arthritis
  • Scale for Testing Muscle Strength Score
  • skin disease
  • spleen disease
  • statistical analysis
  • thrombocytopenia
  • treatment outcome
  • vasculitis

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