Study of Glutathione, Vitamin C and Cysteine in Children With Autism and Severe Behavior Problems

Study Overview
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Brief Summary
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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
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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.

Official Title
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Double-Blind, Placebo-Controlled, Crossover Study of Glutathione, Vitamin C and Cysteine in Children With Autism and Severe Behavior Problems

Conditions
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Autism, Severe Behavior Disorder

Intervention / Treatment
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* Drug: placebo
* Drug: glutathione
* Drug: glutathione, vit C and NAC


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Randomized to placebo or treatment (glutathione or glutathione/vit C/NAC) | Drug: placebo<br>* 50 mL of 1/2 normal saline IV<br>|
| Active Comparator: Glutathione<br>Randomized to placebo or treatment (glutathione or glutathione/vit C/NAC) | Drug: glutathione<br>* glutathione 600 mg IV<br>|
| Active Comparator: Glutathione, Vit C and NAC<br>Randomized to placebo or treatment (glutathione or glutathione/vit C/NAC) | Drug: glutathione, vit C and NAC<br>* Glutathione 600 mg IV Vitamin C 2000 mg IV N-acetylcysteine 20 mg/kg IV (max dose = 600 mg) Mix above three in 1/2 NS for a total volume of 50 mL<br>* Other names: NAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Improvement in both developmental skills and behavior measured using validated scales in subjects receiving either glutathione, glutathione/Vitamin C/N-acetylcysteine or placebo measured at baseline, 9 weeks and at the end of study in a double-blind cross-over design. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio |  | Baseline | 
| Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio |  | 9 weeks | 
| Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio |  | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism, Severe Behavior Disorder, Glutathione, Antioxidants