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

This study has been completed.
Sponsor:
Collaborators:
Kosair Children's Hospital Foundation
Cumberland Pharmaceuticals
Information provided by (Responsible Party):
University of Louisville
ClinicalTrials.gov Identifier:
NCT00889538
First received: April 28, 2009
Last updated: May 23, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention
Autism
Severe Behavior Disorder
 Drug: placebo
Drug: glutathione
Drug: glutathione, vit C and NAC

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled, Crossover Study of Glutathione, Vitamin C and Cysteine in Children With Autism and Severe Behavior Problems

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • 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. [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Response to glutathione (changes in behavior) will correlate with the glutathione level (GSH) and GSH:GSSG ratio [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

  Eligibility

Ages Eligible for Study:   5 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00889538

Locations
United States, Kentucky
KCPCRU
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
Kosair Children's Hospital Foundation
Cumberland Pharmaceuticals
Investigators
Principal Investigator: Patricia G. Williams, MD University of Louisville
Study Director: Janice E. Sullivan, M.D. University of Louisville
  More Information

No publications provided

Responsible Party: University of Louisville
ClinicalTrials.gov Identifier: NCT00889538     History of Changes
Other Study ID Numbers: Glutathione-KCPCRU-01
Study First Received: April 28, 2009
Last Updated: May 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Louisville:
Autism
Severe Behavior Disorder
Glutathione
Antioxidants

Additional relevant MeSH terms:
Autistic Disorder
Mental Disorders
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Ascorbic Acid
Vitamins
Antioxidants
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on May 23, 2013