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

April 13, 2015 updated by: Yolanda de Diego Otero

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Malaga, Spain, 29009
        • Psychiatric Service. Hospital Carlos Haya

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Dietary supplement: Placebo
Two daily dose of placebo, administered at breakfast and dinner for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, week 12, week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline, week 12 and week 24
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
baseline, week 12 and week 24
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:

  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.
Baseline, week 12 and week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yolanda de Diego Otero

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

March 29, 2011

First Submitted That Met QC Criteria

April 5, 2011

First Posted (Estimate)

April 6, 2011

Study Record Updates

Last Update Posted (Estimate)

April 14, 2015

Last Update Submitted That Met QC Criteria

April 13, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2009-017837-23

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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