Safety and Efficacy Study of Antioxidants for the Treatment of the Fragile X Syndrome (SXF-TRA152)
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.
|Fragile X Syndrome||Dietary Supplement: Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E) Dietary Supplement: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official 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|
- 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.
- 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
- 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
- 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:
- 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.
|Study Start Date:||December 2010|
|Study Completion Date:||April 2015|
|Primary Completion Date:||April 2015 (Final data collection date for primary outcome measure)|
Experimental: Ascorbic Acid and alpha-tocopherol
Two daily doses of the combination of antioxidants, administered at breakfast and dinner
Dietary Supplement: Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E)
Placebo Comparator: Placebo
Two daily doses of placebo, administered at breakfast and dinner
Dietary Supplement: Placebo
Two daily dose of placebo, administered at breakfast and dinner for 12 weeks
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01329770
|Psychiatric Service. Hospital Carlos Haya|
|Malaga, Spain, 29009|
|Principal Investigator:||Yolanda de Diego Otero, PhD||IMABIS Foundation. Hospital Carlos Haya. Malaga|
|Principal Investigator:||Lucia M Perez Costillas, MD PhD||Hospital Carlos Haya. Malaga|