title: A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.
abstract: BACKGROUND
  Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment.
  
  
  METHODS
  A phase II randomized, double-blind pilot clinical trial.
  
  
  METHODS
  male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria.
  
  
  METHODS
  clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment.
  
  
  CONCLUSIONS
  A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011).
authors.affiliation: Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Civil, Pabellón 2 bajo, Plaza del Hospital Civil S/N, 29009 Málaga, Spain. yolanda.diego.exts@juntadeandalucia.es.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Diego-Otero
authors.forename: Rocio
authors.initials: R
authors.lastname: Calvo-Medina
authors.forename: Carolina
authors.initials: C
authors.lastname: Quintero-Navarro
authors.forename: Lourdes
authors.initials: L
authors.lastname: Sánchez-Salido
authors.forename: Francisco
authors.initials: F
authors.lastname: García-Guirado
authors.forename: Ignacio
authors.initials: I
authors.lastname: del Arco-Herrera
authors.forename: Isabel
authors.initials: I
authors.lastname: Fernández-Carvajal
authors.forename: Teresa
authors.initials: T
authors.lastname: Ferrando-Lucas
authors.forename: Rafaela
authors.initials: R
authors.lastname: Caballero-Andaluz
authors.forename: Lucia
authors.initials: L
authors.lastname: Pérez-Costillas
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects; D041923:Adolescent Development / Q000187:drug effects; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D057189:Checklist; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D002657:Child Development / Q000187:drug effects; D002985:Clinical Protocols; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005600:Fragile X Syndrome / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D010865:Pilot Projects; D012107:Research Design; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D014888:Wechsler Scales; D024502:alpha-Tocopherol / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004338:Drug Combinations; D024502:alpha-Tocopherol; D001205:Ascorbic Acid