Silvia Romano1, Giulia Coarelli1, Christian Marcotulli2, Luca Leonardi2, Francesca Piccolo2, Maria Spadaro3, Marina Frontali3, Michela Ferraldeschi1, Maria Chiara Vulpiani4, Federica Ponzelli1, Marco Salvetti5, Francesco Orzi1, Antonio Petrucci6, Nicola Vanacore7, Carlo Casali2, Giovanni Ristori8. 1. Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Neurosciences, Mental Health, and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy. 2. Department of Medical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy. 3. National Research Council, Institute of Translational Pharmacology, Rome, Italy. 4. Physical Medicine and Rehabilitation Unit, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. 5. Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Neurosciences, Mental Health, and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy. Electronic address: marco.salvetti@uniroma1.it. 6. Neuromuscular and Neurological Rare Diseases Center ASO San Camillo-Forlanini, Rome, Italy. 7. National Centre of Epidemiology, National Institute of Health, Rome, Italy. 8. Center for Experimental Neurological Therapies, Sant'Andrea Hospital, Neurosciences, Mental Health, and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy. Electronic address: giovanni.ristori@uniroma1.it.
Abstract
BACKGROUND: Our previous study in patients with cerebellar ataxias of different causes showed significant benefit of riluzole after 8 weeks. We aimed to confirm these results in patients with spinocerebellar ataxia or Friedreich's ataxia in a 1-year trial. METHODS:Patients with spinocerebellar ataxia or Friedreich's ataxia (2:1 ratio) from three Italian neurogenetic units were enrolled in this multicentre, double-blind, placebo-controlled trial, and randomly assigned to riluzole (50 mg orally, twice daily) or placebo for 12 months. The randomisation list was computer-generated and a centralised randomisation system was implemented. Participants and assessing neurologists were masked to treatment allocation. The primary endpoint was the proportion of patients with improved Scale for the Assessment and Rating of Ataxia (SARA) score (a drop of at least one point) at 12 months. An intention-to-treat analysis was done. This trial is registered at ClinicalTrials.gov, number NCT01104649. FINDINGS:Between May 22, 2010, and Feb 25, 2013, 60 patients were enrolled. Two patients in the riluzole group and three in the placebo group withdrew their consent before receiving treatment, so the intention-to-treat analysis was done on 55 patients (19 with spinocerebellar ataxia and nine with Friedreich's ataxia in the riluzole group, and 19 with spinocerebellar ataxia and eight with Friedreich's ataxia in the placebo group). The proportion with decreased SARA score was 14 (50%) of 28 patients in the riluzole group versus three (11%) of 27 in the placebo group (OR 8·00, 95% CI 1·95-32·83; p=0·002). No severe adverse events were recorded. In the riluzole group, two patients had an increase in liver enzymes (less than two times above normal limits). In two participants in the riluzole group and two participants in the placebo group, sporadic mild adverse events were reported. INTERPRETATION: Our findings lend support to the idea that riluzole could be a treatment for cerebellar ataxia. Longer studies and disease-specific trials are needed to confirm whether these findings can be applied in clinical practice. FUNDING: Agenzia Italiana del Farmaco.
RCT Entities:
BACKGROUND: Our previous study in patients with cerebellar ataxias of different causes showed significant benefit of riluzole after 8 weeks. We aimed to confirm these results in patients with spinocerebellar ataxia or Friedreich's ataxia in a 1-year trial. METHODS:Patients with spinocerebellar ataxia or Friedreich's ataxia (2:1 ratio) from three Italian neurogenetic units were enrolled in this multicentre, double-blind, placebo-controlled trial, and randomly assigned to riluzole (50 mg orally, twice daily) or placebo for 12 months. The randomisation list was computer-generated and a centralised randomisation system was implemented. Participants and assessing neurologists were masked to treatment allocation. The primary endpoint was the proportion of patients with improved Scale for the Assessment and Rating of Ataxia (SARA) score (a drop of at least one point) at 12 months. An intention-to-treat analysis was done. This trial is registered at ClinicalTrials.gov, number NCT01104649. FINDINGS: Between May 22, 2010, and Feb 25, 2013, 60 patients were enrolled. Two patients in the riluzole group and three in the placebo group withdrew their consent before receiving treatment, so the intention-to-treat analysis was done on 55 patients (19 with spinocerebellar ataxia and nine with Friedreich's ataxia in the riluzole group, and 19 with spinocerebellar ataxia and eight with Friedreich's ataxia in the placebo group). The proportion with decreased SARA score was 14 (50%) of 28 patients in the riluzole group versus three (11%) of 27 in the placebo group (OR 8·00, 95% CI 1·95-32·83; p=0·002). No severe adverse events were recorded. In the riluzole group, two patients had an increase in liver enzymes (less than two times above normal limits). In two participants in the riluzole group and two participants in the placebo group, sporadic mild adverse events were reported. INTERPRETATION: Our findings lend support to the idea that riluzole could be a treatment for cerebellar ataxia. Longer studies and disease-specific trials are needed to confirm whether these findings can be applied in clinical practice. FUNDING: Agenzia Italiana del Farmaco.
Authors: Tanya V Aranca; Tracy M Jones; Jessica D Shaw; Joseph S Staffetti; Tetsuo Ashizawa; Sheng-Han Kuo; Brent L Fogel; George R Wilmot; Susan L Perlman; Chiadi U Onyike; Sarah H Ying; Theresa A Zesiewicz Journal: Neurodegener Dis Manag Date: 2016
Authors: Xiaofei Du; Joao L Carvalho-de-Souza; Cenfu Wei; Willy Carrasquel-Ursulaez; Yenisleidy Lorenzo; Naileth Gonzalez; Tomoya Kubota; Julia Staisch; Timothy Hain; Natalie Petrossian; Michael Xu; Ramon Latorre; Francisco Bezanilla; Christopher M Gomez Journal: Proc Natl Acad Sci U S A Date: 2020-03-04 Impact factor: 11.205