Safety and Efficacy Study of Antioxidants for the Treatment of the Fragile X Syndrome
Condition: Fragile X Syndrome
MeSH terms: Fragile X Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The Fragile X syndrome (FXS) was first described by Dr. Martin and Dr. Bell in 1943, in
      families with several patients affected by sex-linked mental disability. This disorder is the
      most common cause of inherited mental disability. The prevalence of the Fragile X syndrome
      has been established at 1 in 2,500 males and 1 in 4000 females.

      Despite moderate to severe mental retardation, fragile X patients exhibit macroorchidism, an
      elongated face, long ears, connective tissue dysplasia, hyperactivity, autistic-like and
      stereotypical behaviours, speech delay and increased sensory sensitivity.

      Objective: To evaluate the effect of the combination of the antioxidant Ascorbic acid and
      tocopherol, as therapy of the Fragile X Syndrome in young males.

      Hypothesis: It is proposed that part of the pathophysiology of the central nervous system in
      the animal model of the fragile X syndrome may be determined by oxidative stress. In
      addition, Fragile X patients showed a significantly low level of ascorbic acid in plasma. The
      biochemical characteristics of oxidative stress may be reversed in the FMR1-KO mice, by a
      chronic treatment with antioxidant compounds such as tocopherol or melatonin, it may also
      normalize several hallmarks of the Syndrome such as hyperactivity, anxiety and cognitive
      deficits. The normalization of the oxidative stress is proposed as a new therapeutic pathway
      to alleviate conditions caused by an excess of free radicals that are crucial in
      neurodevelopmental diseases such as autism, down syndrome and other diseases of the central
      nervous system.
    

Detailed description: 
      -  Objective: To evaluate the effect of the combination of the antioxidant Ascorbic acid
           and tocopherol, as therapy of the Fragile X Syndrome in young males.

        -  Design: Pilot clinical trial, Phase II , 6-month randomized, double-blind
           placebo-controlled one-way crossover clinical trial, with two treatment periods of 12
           weeks duration.

        -  Setting: IMABIS Foundation. Carlos Haya Hospital, Malaga.

        -  Subjects: Children aged 5-11 years (infants) and 12-18 years (adolescents) diagnosed
           with Fragile X syndrome.

        -  Intervention: 30 participants randomly assigned, to receive antioxidant vitamins C
           (ascorbic acid) and vitamin E (d-alpha-tocopherol) once a day or placebo for 12 weeks
           double-blind. In Study Period 2, all participants receive (open) active treatment.
           Outcome measures: improvement in plasma antioxidant levels, oxidative stress (indicated
           by glutathione status, thiobarbituric acid reacting substances (TBARS) and carbonyl
           content of proteins) and HPA axis response. Behavioral problems will be studied using
           "Developmental behavior checklist" and "Teacher's and Parent´s Questionnaire, C. Keith
           Conners", also learning improvement will be analyzed using "Wechsler Intelligence Scale
           for children" at 0, 3, 6 months during the trial and 3 months after completing the
           treatment.
    

Intervention name(s): Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E); Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Vitamin E (D-alpha-Tocopherol) 10 mg/kg/day (with a maximum of 600mg/day)
Vitamin C (L-Ascorbic Acid) 10 mg/kg/day (with a maximum of 800mg/day) For 12 weeks; Two daily dose of placebo, administered at breakfast and dinner for 12 weeks
Intervention MeSH terms: Vitamins; Ascorbic Acid; Vitamin E; Tocopherols; alpha-Tocopherol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neurodevelopmental disability; Hyperactivity; Anxiety; Cognitive problems; Behavioural symptoms; Fragile X syndrome; Autism; inherited Genetic condition