Clinical trial NCT00889538: Study of Glutathione, Vitamin C and Cysteine in Children With Autism and Severe Behavior Problems
Official title: Double-Blind, Placebo-Controlled, Crossover Study of Glutathione, Vitamin C and Cysteine in Children With Autism and Severe Behavior Problems
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism
Severe Behavior Disorder
Keywords: Autism
Severe Behavior Disorder
Glutathione
Antioxidants
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: Cumberland Pharmaceuticals
name: Norton Healthcare
First posted: 2009-04-29
Enrollment: 24
Sex: ALL
Minimum age (years): 5
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a double-blind, placebo-controlled crossover study to evaluate the safety and efficacy of glutathione alone or glutathione, vitamin C and NAC treatment in children with autism who also have severe behavior problems. The investigators hypothesis is that children with autism will show improvement in both learning capabilities and behavior with either glutathione, or glutathione, vitamin C and NAC therapy.

Detailed description: This is a prospective, single center, double-blind, randomized pilot study in children and adolescents with autism and severe behavior disorders. All subjects will undergo initial screening procedures to determine eligibility. They will then be randomized to either 8 weeks of placebo or 8 weeks of glutathione or glutathione, vitamin C and N-acetylcysteine. They will receive intravenous treatment weekly and will have ongoing behavioral studies during this period. Following 8 weeks of therapy, they will have a week without treatment then will cross-over to the alternate therapy for weekly intravenous infusions and behavioral testing. In addition to baseline hematology and chemistries, baseline oxidized and reduced glutathione will be measured. These parameters will be repeated at the end of each 8 week course of therapy.

Eligibility criteria: Inclusion Criteria:

* Age 5 to 16 years, inclusive
* Diagnosed with autism using the ADI-R (Autism Diagnostic Interview-Revised)
* ABC Irritability/Agitation subscale score (Aberrant Behavior Checklist Subscale) ≥ 18
* CGI-S score (Clinical Global Impression-Severity Scale) ≥ 4
* Must be drug naïve or on a stable dose of medication(s) and educational/behavioral interventions for one month prior to participation
* Parent/legal guardian must provide written consent and required research authorization (i.e. HIPAA) prior to the performance of any study procedures.

Exclusion Criteria:

* Presence of another disorder on the autism spectrum including PDD-NOS (Pervasive Developmental Disorder Not Otherwise Specified), Asperger's, and Rett's Syndrome
* Patient with a known cause of autism such as Fragile X
* Evidence of significant renal dysfunction (e.g. GFR estimated by the Schwartz formula \< 50 mL/min or serum creatinine \> 2.5 X upper limit of normal for age)
* Evidence of significant hepatic dysfunction (serum transaminases \> 2.5 X the upper limit of normal)
* Known hypersensitivity to glutathione, vitamin C or NAC
* Pregnant or lactating female
* Inability of subject and parent to be able to comply with requirements for study visits and procedures
* Presence of major mental illness
* History of antioxidant supplementation.

Primary outcomes:
measure: Improvement in both developmental skills and behavior with either glutathione or glutathione, Vitamin C and N-acetylcysteine therapy as compared to placebo therapy. Subjects will also be monitored using clinical and laboratory safety parameters.
timeFrame: 4 months
Secondary outcomes:
measure: Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio
timeFrame: Baseline
measure: Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio
timeFrame: 9 weeks
measure: Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Louisville
country: United States
facility: KCPCRU
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Patricia G. Williams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Louisville
name: Janice E. Sullivan, M.D.
role: STUDY_DIRECTOR
References: