title: Deferiprone in Friedreich ataxia: a 6-month randomized controlled trial.
abstract: OBJECTIVE
  We conducted a 6-month, randomized, double-blind, placebo-controlled study to assess safety, tolerability, and efficacy of deferiprone in Friedreich ataxia (FRDA).
  
  
  METHODS
  Seventy-two patients were treated with deferiprone 20, 40, or 60mg/kg/day or placebo, divided into 2 daily doses. Safety was the primary objective; secondary objectives included standardized neurological assessments (Friedreich Ataxia Rating Scale [FARS], International Cooperative Ataxia Rating Scale [ICARS], 9-Hole Peg Test [9HPT], Timed 25-Foot Walk, Low-Contrast Letter Acuity), general functional status (Activities of Daily Living), and cardiac assessments.
  
  
  RESULTS
  Deferiprone was well tolerated at 20mg/kg/day, whereas more adverse events occurred in the 40mg/kg/day than in the placebo group. The 60mg/kg/day dose was discontinued due to worsening of ataxia in 2 patients. One patient on deferiprone 20mg/kg/day experienced reversible neutropenia, but none developed agranulocytosis. Deferiprone-treated patients receiving 20 or 40mg/kg/day showed a decline in the left ventricular mass index, compared to an increase in the placebo-treated patients. Patients receiving 20mg/kg/day of deferiprone had no significant change in FARS, similar to the placebo-treated patients, whereas those receiving 40mg/kg/day had worsening in FARS and ICARS scores. The lack of deterioration in the placebo arm impaired the ability to detect any potential protective effect of deferiprone. However, subgroup analyses in patients with less severe disease suggested a benefit of deferiprone 20mg/kg/day on ICARS, FARS, kinetic function, and 9HPT.
  
  
  CONCLUSIONS
  This study demonstrated an acceptable safety profile of deferiprone at 20mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20mg/kg/day may reduce disease progression, whereas higher doses appear to worsen ataxia.
authors.affiliation: Department of Neurology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pandolfo
authors.forename: Javier
authors.initials: J
authors.lastname: Arpa
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: Kim Hanh
authors.initials: KH
authors.lastname: Le Quan Sang
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Irene
authors.initials: I
authors.lastname: Sanz-Gallego
authors.forename: Geneieve
authors.initials: G
authors.lastname: Tai
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Michael
authors.initials: M
authors.lastname: Spino
authors.forename: Fernando
authors.initials: F
authors.lastname: Tricta
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D000077543:Deferiprone; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005621:Friedreich Ataxia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D011728:Pyridones / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology; D055815:Young Adult
chemical_list: D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone