The goal of this study is to target the neurobiology of restricted and repetitive behaviors in children with autism spectrum disorder using N-acetylcysteine (NAC), a well-tolerated nutritional supplement that has shown promise for reducing symptom severity in recent small-scale trials. The findings from this research will shed light on the mechanisms of action underlying the clinical benefits of NAC and the effects of NAC on altering restricted and repetitive behavior symptom severity in children with autism spectrum disorder. This is a 12-week double-blind, randomized, placebo-controlled trial of NAC.

Inclusion Criteria:

• children between 3 years and 12 years 11 months
• diagnosis of autism spectrum disorder confirmed with the Autism Diagnostic Interview- Revised and the Autism Diagnostic Observation Schedule-2, Brief Observation of Symptoms of Autism, or Childhood Autism Rating Scale
• at least moderate severity of restricted and repetitive behaviors defined by a Children's Yale-Brown Obsessive Compulsive Scale for Autism Spectrum Disorder score ≥ 11
• physical development indicative of prepubescence as defined by criteria for Tanner Stage 1
• if home address is within 300 miles of the primary study site, participants must pass MR safety screening (e.g., no metal in the body) and attempt baseline neuroimaging (MRI or EEG), otherwise baseline neuroimaging is not required for participation
• have stable medication regimens (≥ 30 days) and psychosocial treatments (≥ 60 days) prior to randomization with no anticipated changes during the trial

Exclusion Criteria:

• presence of known genetic abnormalities associated with ASD (e.g. Fragile X)
• current or life-time diagnosis of severe psychiatric disorder (e.g., schizophrenia)
• presence of significant medical problems
• the inability of at least one caregiver to speak and read English to a sufficient level
• participants taking glutathione agents/prodrugs
• history of any adverse effects to glutathione agents/prodrugs
• the inability to drink a sample study compound dissolved in liquid

De-Identified data will be shared with the National Database for Autism Research (NDAR)

The data will be shared on January 15th and July 15th each year

Researchers with access to the National Database for Autism Research (NDAR) will be able to obtain the submitted data

The placebo compound will match the active N-acetylcysteine in appearance, odor, taste, and packaging.