Clinical Trial for Asses the Safety and Efficacy of Vitamin C and Vitamin E in Combination Versus Placebo for Treating Cognitive and Behavior Disorder in Children With Fragile X Syndrome (SXF2-8)

Clinical Trials Phase III, Double Blind, Crossover to Asses the Safety and Efficacy of Vitamin C and Vitamin E in Combination Versus Placebo for Treating Cognitive and Behavior Disorder in Children With Fragile X Syndrome

The purpose of this study is to determine vitamin C and vitamin E in combination are effective in the treatment of cognitive and behavior disorder in children with fragile X syndrome.

Study Overview

• Status: Completed
• Conditions: X Fragile Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Vitamin C 10mg/Kg Vitamin E 10 mg/Kg

Detailed Description

The combination of vitamin E and vitamin C supplementation has been associated with a lower prevalence (-78%) and incidence (-64%) of Alzheimer's disease in the elderly population. It has recently been shown that dietary vitamin E supplementation reduces the production of free radicals inhibiting NADPH oxidase activity in circulating neutrophils. Another work describes the inhibition of glutamate release by activated microglia in cell cultures incubated with vitamin E, effect that can prevent excitotoxicity.

The investigators propose to evaluate the effectiveness of treatment in neurodevelopmental disorders affected by fragile X syndrome (FXS) with lipophilic compounds antioxidants such as tocopherol and hydrophilic compounds antioxidants such as ascorbic acid, which regulate oxidative stress and improve learning and behavioral mouse model and humans.

Our group has positive results in the use of this combination of antioxidants as a treatment for fragile X syndrome in adolescents. This disease has developed previous clinical trials with EUDRACT codes: 2009-017837-23 and 2013-004276-35.

The use of the combination of vitamin C and E in the treatment of cognitive and behavioral disorder in FXS, is patented PCT-050 187 with reference number 2011070875

This combination will be administered as a single oral dose with a total dose of 10mg / kg / day for each of the vitamins. This dose is maintained within the therapeutic range of both antioxidants.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Málaga
    • Malaga, Málaga, Spain, 29009
      • Hospital Regional de Malaga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Fragile X syndrome by genetic testing of molecular biology, full mutation result methylation.
2. Having an older age of 1 year and less than 9 years
3. Having signed the informed consent document before starting their participation in the trial.

Exclusion Criteria:

1. Any advanced, severe or unstable disease.
2. Individuals with other psychiatric diagnosis as the first diagnosis.
3. It have been suffered serious medical problems in the last 12 months.
4. Be taking more than 100 mg of vitamin E or C a day in the last month.
5. Having physical, mental or sensory impairments that prevent the assessment of effectiveness.
6. Hypersensitivity to any component of the preparation.
7. Liver failure or severe renal or previous history of kidney stones.
8. Any treatment regimen, including treatment with psychotropic drugs and / or anticonvulsant therapy that has not been stable for a period ≥ 4 weeks before randomization.
9. Current treatment with more than two psychoactive medications, excluding medication used specifically for the control of seizures.
10. Hypoprothrombinemia secondary to vitamin K deficiency
11. Sensitivity to any of the compounds of formula treatment.
12. Patients diagnosed with congenital or idiopathic methemoglobinemia for diagnosis of glucose-6-phosphate dehydrogenase deficiency.
13. Use of oral anticoagulants, iron or vitamin A.
14. Forecast initiate or change pharmacological or no pharmacological interventions during the course of the study.
15. Patients weighing less than 4.2 kg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin C 10 mg/Kg + Vitamin E 10 mg/Kg; Vitamin C and Vitamin E supplementation 10 mg/kg/ day	Drug: Vitamin C 10mg/Kg Vitamin E 10 mg/Kg
Placebo Comparator: Placebo; Placebo solution	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Autism Treatment Evaluation Checklist (ATEC).	32 weeks
Global Clinical Impression (GCI)	32 weeks
Peabody Picture Vocabulary Test (PiVT)	32 weeks
Battelle developmental inventory screening	32 weeks
Vineland Adaptive Behavior Scales	32 weeks
Adverse event reported	32 weeks
Quantitative Checklist for Autism in Toddlers (Q-Chat) test	32 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Golberg scale GHQ-28	32 weeks
Quality life SF36 test	32 weeks
Psychological General Well-Being Index	32 weeks
Sleep Disturbance Scale for Children	32 weeks

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Collaborators: Delos Clinical

Publications and helpful links

General Publications

• Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, Norton MC, Welsh-Bohmer KA, Breitner JC; Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004 Jan;61(1):82-8. doi: 10.1001/archneur.61.1.82.
• Castilla P, Davalos A, Teruel JL, Cerrato F, Fernandez-Lucas M, Merino JL, Sanchez-Martin CC, Ortuno J, Lasuncion MA. Comparative effects of dietary supplementation with red grape juice and vitamin E on production of superoxide by circulating neutrophil NADPH oxidase in hemodialysis patients. Am J Clin Nutr. 2008 Apr;87(4):1053-61. doi: 10.1093/ajcn/87.4.1053.
• Barger SW, Goodwin ME, Porter MM, Beggs ML. Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation. J Neurochem. 2007 Jun;101(5):1205-13. doi: 10.1111/j.1471-4159.2007.04487.x. Epub 2007 Mar 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): September 25, 2017
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: October 7, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: behavior, cognitive
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Mental Disorders; Fragile X Syndrome; Child Behavior Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Antioxidants; Vitamin E; Vitamins; Ascorbic Acid
• Other Study ID Numbers: SXF2-8