A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders

Autism is increasingly being recognized as a common disorder with enormous public health
significance. The core symptoms of autism include severe deficits in social relatedness and
communication, and interfering repetitive behavior. No medications have been shown to
consistently improve any of these symptoms.

The central hypothesis of this study is that NAC will improve behavioral manifestations of
autism which may include core or associated symptoms. We plan to test our hypothesis and
complete the objectives of this project by pursuing the following specific aims:

- Evaluate the efficacy of oral NAC in a 12-week, double-blind, placebo-controlled study
involving 32 children and adolescents with autism spectrum disorders.

- Evaluate the safety and tolerability of oral NAC in 32 children and adolescents with
autism spectrum disorders.

Inclusion Criteria:

- Age 4 to 12 years.

- Diagnosis of autistic disorder, Asperger's disorder, or PDD NOS.

- If taking concomitant psychotropic medications, the medication must be at a constant
dose for 60 days with no dose changes planned for the duration of the trial.

- Able to swallow capsules.

Exclusion Criteria:

- Presence of any medical condition that significantly increases risk or hampers
assessment (e.g., unstable hypertension or cardiac disease, unstable asthma, kidney
disease, unstable seizure disorder, pregnancy or any other medical condition as
determined by the investigator).

- Weight < 15 kg.

- Subjects taking concomitant medications or supplements known for their glutamatergic
effects (e.g., dextromethorphan, D-cycloserine, amantadine, memantine, lamotrigine,
riluzole) or antioxidant properties (high dose vitamin supplements, DMG, TMG, many
alternative treatments) within 30 days of the baseline visit with the exception of
short term use of dextromethorphan as needed as a cough suppressant. The use of this
medicine must be stopped at least 7 days prior to the baseline visit. Regular
multivitamins will be allowed.

- Subjects taking daily acetaminophen or nonsteroidal anti-inflammatory drugs within 30
days of the baseline visit.

- Profound mental retardation as evidenced by a mental age below 18 months.

- Subjects taking concomitant medications with the potential for pharmacokinetic or
pharmacodynamic drug-drug interactions (e.g., carbamazepine) within 30 days of the
baseline visit.

- Subjects who are likely to experience significant changes in their ongoing
psychosocial or medical treatments for autism over the course of the trial (e.g.,
initiation of new behavioral therapy, initiation of new medication or alternative
treatment [e.g., chelation]). Minor changes in ongoing treatment (e.g., missed therapy
sessions due to holiday/vacation; planned break in therapy due to school holidays)
will not be considered significant.

- History of prior treatment with NAC.

- Evidence of hypersensitivity/allergy to NAC.

- Presence of certain neurodevelopmental disorders such as Fragile X Syndrome, Tuberous
Sclerosis, or other neurological disorders known to be associated with autism or
autistic features.

- Diagnosis of Rett's disorder, childhood disintegrative disorder, schizophrenia,
bipolar disorder, another psychotic disorder, or substance abuse disorder.