Folate Rechallenge

NCT00672360 | Completed Phase 2

• 1 other identifier: H-20959
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

New evidence suggests that autistic disorder (AD) may be associated with abnormalities in folate metabolism, which is a process that affects genetic expression by facilitating the formation of methyl donors for DNA methylation. Limited data show that some children with AD show behavioral improvements with folic acid (FA) therapy, while others show a worsening effect. If behavioral worsening is linked with abnormalities in folate metabolism, then nutritional modifications could normalize these processes and result in clinical improvements. To address this premise, we propose a randomized, placebo-controlled crossover pilot study with two phases. The first phase will focus on the behavioral and biochemical responses of children with AD to high-dose folic acid supplementation. Because FA is an inactive folate that requires biochemical conversion to become active, and select genotypes impede this conversion, our general hypothesis is that FA will yield behavioral improvements in some children but exacerbate problem behaviors in others. During the second phase, children who had a worsened behavioral response to FA during phase 1 will participate in an open-label trial of high-dose Metafolin® supplementation. The focus here would similarly be on the behavioral and biochemical outcomes of participating children following treatment with the study supplement. Because Metafolin® is an active folate metabolite that should not be affected by genotypes in the folate pathway, our general hypothesis for phase 2 is that Metafolin® would yield behavioral improvements without the risk for behavioral worsening. Results from this project may provide support for continued study of the potential relationship between folate metabolism and problem behaviors among children with AD, potentially justifying the need to examine effects of folate supplementation among a larger sample of affected children.

Conditions

Autism

Keywords

Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (1)

• Behavior as measured with the Aberrant Behavior Checklist (ABC) and the Pervasive Developmental Disorder Behavior Inventory (PDDBI).

  Pre-, mid-, and post-treatment during each phase (folic acid and placebo).

Secondary Outcomes (1)

• Level of folate metabolites in plasma and site-specific DNA methylation.

  Pre- and post-treatment during each phase (folic acid and placebo).

Study Arms (2)

1

EXPERIMENTAL

Dietary Supplement: Folic acid

2

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Folic acid DIETARY_SUPPLEMENT

Compounded capsule, 7.6mg, taken orally, twice daily for 4 weeks.

Also known as: folate

1

Placebo DIETARY_SUPPLEMENT

Compounded capsule of NaCl, taken orally, twice daily for 4 weeks.

2

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Child participant has a confirmed diagnosis of AD by Autism Diagnostic Observation Schedule and Autism Diagnostic Interview--Revised criteria
• Child participant is in stable condition with relatively good control of seizures and no other significant medical problems, including liver, kidney, or heart problems, at the time of entrance to the study. If the child participant is taking medication for a seizure disorder, the investigators will assess his/her eligibility with particular regard to type of seizure medication and other health-related information gleaned during the medical examination
• Child participant and parents are willing to comply with the proposed treatments
• Child participant is able to take oral medication
• Family is fluent in the English language
• Parent/caregiver agrees to provide behavioral data on participating children at the requested time points
• Family agrees to be contacted weekly by study personnel during the treatment phases

You may not qualify if:

• Child participant has co-morbid medical and/or genetic disorders, including celiac disease
• Child participant has a history of liver or renal disease
• Child participant is currently being treated for a serious acute illness
• Child participant has a known allergy to any of the proposed supplements
• Child participant has uncontrolled seizures
• Child participant meets criteria for Asperger's syndrome, PDD-NOS, or does not meet strict criteria for AD
• Family is not proficient in the English language

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Mol. & Human Gen./Beaudet Lab

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: May 6, 2008
• Study Start: May 1, 2007
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

US (1)