Fragile X SyndromePhase 2SXF-TRA152NCT01329770
Safety and Efficacy Study of Antioxidants for the Treatment of the Fragile X Syndrome
A Phase 2 study testing Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E) in people with Fragile X Syndrome, run by Yolanda de Diego Otero at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 18 years, men only
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSpain
- Study dates
- Dec 2010to Apr 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Fragile X Syndrome
- Being tested
- Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E), Placebo
- Keywords
- Neurodevelopmental disability, Hyperactivity, Anxiety, Cognitive problems, Behavioural symptoms, Fragile X syndrome, Autism, inherited Genetic condition
- Medical subject headings
- Fragile X Syndrome, Spasm, Anxiety Disorders, Behavioral Symptoms, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
PlaceboDietary supplement
Two daily dose of placebo, administered at breakfast and dinner for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ascorbic Acid and alpha-tocopherol | Experimental | Two daily doses of the combination of antioxidants, administered at breakfast and dinner Receives: Dietary Supplement: Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E) |
| Placebo | Placebo comparator | Two daily doses of placebo, administered at breakfast and dinner Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Inventory of behaviour development (DBC-P24) will be realized before starting, 12 weeks and 24 weeks after beginning the treatment
Measured: Baseline, week 12 and week 24
Wechsler Intelligence Scale for children
Wechsler Intelligence Scale for children will be used at base line and 12 weeks after beginning the treatment
Measured: baseline, week 12 and week 24
Composite measure of blood and urine.
Safety Evaluation through blood and urine measurement. The following studies will be done at base line, 12 and 24 weeks after beginning the treatment:
- Hematology
- Biochemical
- 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.
Measured: Baseline, week 12 and week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2011 (estimated)
- Study startDec 2010
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yolanda de Diego Otero
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Yolanda de Diego Otero, The Mediterranean Institute for the Advance of Biotechnology and Health Research
- Investigators
- Yolanda de Diego Otero, PhD, Principal investigator, IMABIS Foundation. Hospital Carlos Haya. MalagaLucia M Perez Costillas, MD PhD, Principal investigator, Hospital Carlos Haya. Malaga
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01329770
- Sponsor's protocol ID
- 2009-017837-23
- Other IDs
- 2009
- Acronym
- SXF-TRA152
- Status last verified
- Apr 2015
- First submitted
- 29 Mar 2011
- Last updated
- 14 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 18843266Romero-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.
PubMed 19141086el 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.
PubMed 18005058de 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.
PubMed 25187257
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01329770
- Acronym / sponsor ID
- SXF-TRA152 / 2009-017837-23
- Conditions
- Fragile X Syndrome
- Keywords
- Neurodevelopmental disability, Hyperactivity, Anxiety, Cognitive problems, Behavioural symptoms, Fragile X syndrome, Autism, inherited Genetic condition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Yolanda de Diego OteroUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 6 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ascorbic Acid and alpha-tocopherol | Experimental | Dietary Supplement: Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E)Two daily doses of the combination of antioxidants, administered at breakfast and dinner |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboTwo daily doses of placebo, administered at breakfast and dinner |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Dietary supplement | Ascorbic Acid and alpha-tocopherol |
| PlaceboTwo daily dose of placebo, administered at breakfast and dinner for 12 weeks | Dietary supplement | Placebo |
Primary outcome
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.
3 secondary outcomes
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
Wechsler Intelligence Scale for children
Time frame: baseline, week 12 and week 24
Composite measure of blood and urine.
Time frame: Baseline, week 12 and week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2015.
- Background: PubMed 18843266de 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.
- Background: PubMed 19141086Romero-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.
- Background: PubMed 18005058el 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.
- Derived from this study: PubMed 25187257de 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.
- Foundation IMABISLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yolanda de Diego Otero, PhD principal investigator
IMABIS Foundation. Hospital Carlos Haya. Malaga
Lucia M Perez Costillas, MD PhD principal investigator
Hospital Carlos Haya. Malaga
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ascorbic Acid (Vitamin C) and Alpha-tocopherol (Vitamin E) in people with Fragile X Syndrome, run by Yolanda de Diego Otero at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the baseline Conner's Parent and Teacher Scales at 12 and 24 weeks (time frame: Baseline, week 12, week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01329770, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2015.