Trial record 4 of 7 for:    FMR1

Safety and Efficacy Study of Antioxidants for the Treatment of the Fragile X Syndrome (SXF-TRA152)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by The Mediterranean Institute for the Advance of Biotechnology and Health Research.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
The Mediterranean Institute for the Advance of Biotechnology and Health Research
ClinicalTrials.gov Identifier:
NCT01329770
First received: March 29, 2011
Last updated: April 5, 2011
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
Fragile X Syndrome
Dietary Supplement: Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E)
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by The Mediterranean Institute for the Advance of Biotechnology and Health Research:

Primary Outcome Measures:
  • Changes in the baseline Conner's Parent and Teacher Scales at 12 and 24 weeks [ Time Frame: Baseline, week 12, week 24 ] [ Designated as safety issue: No ]
    Hyperactivity scales: Conners Parent and Teacher Questionnaire, realized before starting treatment, 12 weeks and 24 weeks after beginning the treament.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Wechsler Intelligence Scale for children will be used at base line and 12 weeks after beginning the treatment

  • Safety Evaluation [ Time Frame: Baseline, week 12 and week 24 ] [ Designated as safety issue: Yes ]

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

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


Enrollment: 30
Study Start Date: December 2010
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
  • 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 Comparator: Placebo
Two daily doses of placebo, administered at breakfast and dinner
Other: Placebo
Two daily dose of placebo, administered at breakfast and dinner for 12 weeks

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.
  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01329770

Locations
Spain
Psychiatric Service. Hospital Carlos Haya
Malaga, Spain, 29009
Sponsors and Collaborators
The Mediterranean Institute for the Advance of Biotechnology and Health Research
Investigators
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
  More Information

Additional Information:
Publications:
Responsible Party: Yolanda de Diego Otero PhD, The Mediterranean Institute for the Advance of Biotechnology and Health Research (IMABIS Foundation)
ClinicalTrials.gov Identifier: NCT01329770     History of Changes
Other Study ID Numbers: 2009-017837-23
Study First Received: March 29, 2011
Last Updated: April 5, 2011
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by The Mediterranean Institute for the Advance of Biotechnology and Health Research:
Neurodevelopmental disability
Hyperactivity
Anxiety
Cognitive problems
Behavioural symptoms
Fragile X syndrome
Autism
inherited Genetic condition

Additional relevant MeSH terms:
Fragile X Syndrome
Mental Retardation, X-Linked
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Antioxidants
Ascorbic Acid
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014