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

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

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.

Study Overview

• Status: Completed
• Conditions: Autism; Severe Behavior Disorder
• Intervention / Treatment: Drug: placebo; Drug: glutathione; Drug: glutathione, vit C and NAC

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • KCPCRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Randomized to placebo or treatment (glutathione or glutathione/vit C/NAC)	Drug: placebo; 50 mL of 1/2 normal saline IV
Active Comparator: Glutathione; Randomized to placebo or treatment (glutathione or glutathione/vit C/NAC)	Drug: glutathione; glutathione 600 mg IV
Active Comparator: Glutathione, Vit C and NAC; Randomized to placebo or treatment (glutathione or glutathione/vit C/NAC)	Drug: glutathione, vit C and NAC; 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; Other Names: NAC

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Louisville
• Collaborators: Norton Healthcare; Cumberland Pharmaceuticals
• Investigators: Principal Investigator: Patricia G. Williams, MD, University Of Louisville; Study Director: Janice E. Sullivan, M.D., University Of Louisville

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: April 28, 2009
• First Submitted That Met QC Criteria: April 28, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 6, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Antioxidants; Autism; Glutathione; Severe Behavior Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Problem Behavior; Mental Disorders; Autistic Disorder
• Other Study ID Numbers: Glutathione-KCPCRU-01