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NCT Number: NCT01329770

Safety and Efficacy Study of Antioxidants for the Treatment of the Fragile X Syndrome

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.

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Key information

Conditions

Fragile X Syndrome Anxiety Disorders Autism Spectrum Disorder Autistic Disorder Behavior Behavioral Symptoms Child Development Disorders, Pervasive Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Genetic Diseases, X-Linked Heredodegenerative Disorders, Nervous System Intellectual Disability Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurodevelopmental Disorders Neurologic Manifestations Neuromuscular Manifestations Pathological Conditions, Signs and Symptoms Sex Chromosome Disorders Signs and Symptoms Spasm X-Linked Intellectual Disability

Age range

6 year–18 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

Psychiatric Service. Hospital Carlos Haya

Málaga, Malaga, 29009, Spain

About this study

  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Molecular genetics diagnosis of the syndrome (number of CGG repeats in the FMR1 gene over 200).
  • Presenting characteristic symptoms of fragile X syndrome.
  • Patients older than 6 years and younger that 19 years.
  • Signed informed consent by parents and/or legal tutor prior to enrolment in the trial.
  • Both parents and patients must commit to participate for the duration of the 30 week trial.

Exclusion criteria

  • The study excludes individuals with other neurological disorders not linked to the syndrome.
  • Patients that have had serious medical problems in the previous 12 months.
  • Are taking more than 100mg of vitamin E or vitamin C daily for the past 4 months.
  • Have physical problems, mental or sensory impairments that preclude the assessment of effectiveness.
  • Hypersensitivity to any component of the preparation.

Treatment and study plan

Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E)

Dietary Supplement
  • 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

Placebo

Dietary Supplement

Two daily dose of placebo, administered at breakfast and dinner for 12 weeks

Primary outcomes

  1. Changes in the baseline Conner's Parent and Teacher Scales at 12 and 24 weeks

    Time frame: Baseline, week 12, week 24

    Hyperactivity scales: Conners Parent and Teacher Questionnaire, realized before starting treatment, 12 weeks and 24 weeks after beginning the treament.

Secondary outcomes

  1. Change in the baseline measure of the Inventory of behaviour development (DBC-P24) at 12 and 24 weeks

    Time frame: Baseline, week 12 and week 24

    Inventory of behaviour development (DBC-P24) will be realized before starting, 12 weeks and 24 weeks after beginning the treatment

  2. Wechsler Intelligence Scale for children

    Time frame: baseline, week 12 and week 24

    Wechsler Intelligence Scale for children will be used at base line and 12 weeks after beginning the treatment

  3. Composite measure of blood and urine.

    Time frame: Baseline, week 12 and week 24

    Safety Evaluation through blood and urine measurement. The following studies will be done at base line, 12 and 24 weeks after beginning the treatment:

    • Hematology
    • Biochemical
    • Determination of adrenal axis.
    • Oxidative status.
    • Analysis of urine density, pH, protein, glucose, ketone bodies, bilirubin, blood, nitrite, urobilinogen, leukocytes, urinary sediment, sodium, chlorine, potassium.

Sponsors and collaborators

Lead sponsor

Yolanda de Diego Otero

Other

Registry information

Official study title

Phase II Double-blind Randomized Placebo-controlled 1-way Crossover Trial to Investigate Safety and Efficacy of the Ascorbic Acid and Tocopherol for the Treatment of the Fragile X Syndrome

Acronym: SXF-TRA152

Important dates

Study start
2010
Primary completion
2015
Study completion
2015
First posted
Apr 6, 2011
Registry last updated
Apr 14, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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