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

NCT01329770 | Completed Phase 2 DMC

• 1 other identifier: 2009-017837-23
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Fragile X Syndrome

Keywords

Neurodevelopmental disability; Hyperactivity; Anxiety; Cognitive problems; Behavioural symptoms; Fragile X syndrome; Autism; inherited Genetic condition

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (3)

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

  Baseline, week 12 and week 24

• Wechsler Intelligence Scale for children

  baseline, week 12 and week 24

• Composite measure of blood and urine.

  Baseline, week 12 and week 24

Study Arms (2)

Ascorbic Acid and alpha-tocopherol

EXPERIMENTAL

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

PLACEBO COMPARATOR

Two daily doses of placebo, administered at breakfast and dinner

Dietary Supplement: Placebo

Interventions

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

Ascorbic Acid and alpha-tocopherol

Placebo DIETARY_SUPPLEMENT

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

Placebo

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yolanda de Diego Otero: lead

Study Sites (1)

Psychiatric Service. Hospital Carlos Haya

Málaga, Malaga, 29009, Spain

Location

Related Publications (4)

• de Diego-Otero Y, Romero-Zerbo Y, el Bekay R, Decara J, Sanchez L, Rodriguez-de Fonseca F, del Arco-Herrera I. Alpha-tocopherol protects against oxidative stress in the fragile X knockout mouse: an experimental therapeutic approach for the Fmr1 deficiency. Neuropsychopharmacology. 2009 Mar;34(4):1011-26. doi: 10.1038/npp.2008.152. Epub 2008 Oct 8.

  PMID: 18843266 BACKGROUND

• Romero-Zerbo Y, Decara J, el Bekay R, Sanchez-Salido L, Del Arco-Herrera I, de Fonseca FR, de Diego-Otero Y. Protective effects of melatonin against oxidative stress in Fmr1 knockout mice: a therapeutic research model for the fragile X syndrome. J Pineal Res. 2009 Mar;46(2):224-34. doi: 10.1111/j.1600-079X.2008.00653.x. Epub 2008 Dec 23.

  PMID: 19141086 BACKGROUND

• el Bekay R, Romero-Zerbo Y, Decara J, Sanchez-Salido L, Del Arco-Herrera I, Rodriguez-de Fonseca F, de Diego-Otero Y. Enhanced markers of oxidative stress, altered antioxidants and NADPH-oxidase activation in brains from Fragile X mental retardation 1-deficient mice, a pathological model for Fragile X syndrome. Eur J Neurosci. 2007 Dec;26(11):3169-80. doi: 10.1111/j.1460-9568.2007.05939.x. Epub 2007 Nov 14.

  PMID: 18005058 BACKGROUND

• de Diego-Otero Y, Calvo-Medina R, Quintero-Navarro C, Sanchez-Salido L, Garcia-Guirado F, del Arco-Herrera I, Fernandez-Carvajal I, Ferrando-Lucas T, Caballero-Andaluz R, Perez-Costillas L. A combination of ascorbic acid and alpha-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial. Trials. 2014 Sep 3;15:345. doi: 10.1186/1745-6215-15-345.

  PMID: 25187257 DERIVED

Related Links

• Foundation IMABIS

MeSH Terms

Conditions

Fragile X Syndrome; Spasm; Anxiety Disorders; Behavioral Symptoms; Autistic Disorder

Interventions

Ascorbic Acid; alpha-Tocopherol; Vitamin E

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Tocopherols; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Yolanda de Diego Otero, PhD

  IMABIS Foundation. Hospital Carlos Haya. Malaga

  PRINCIPAL INVESTIGATOR

• Lucia M Perez Costillas, MD PhD

  Hospital Carlos Haya. Malaga

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MSc PhD

Study Record Dates

• First Submitted: March 29, 2011
• First Posted: April 6, 2011
• Study Start: December 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 14, 2015

Record last verified: 2015-04

Locations

ES (1)