Targeting the Neurobiology of RRB in Autism Using N-acetylcysteine: Open Label

Study Overview
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Brief Summary
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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.

Official Title
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Targeting the Neurobiology of Restricted and Repetitive Behaviors in Children With Autism Using N-acetylcysteine: an Open Label Extension

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: N-acetylcysteine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Inclusion criteria: successful completion of IRB protocols 54931 or 68353. Inclusion for 54931 include: individuals between 3 years and 13 years and 11 months at the time of consent 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 in ASD score ≥ 11 physical development indicative of prepubescence as defined by criteria for Tanner Stage 1 medically stable passes MR safety screening (e.g., no metal in the body). Inclusion for 65821: same criteria as above for 54931 have stable medication regimens (≥ 30 days) and psychosocial treatments (≥ 60 days) prior to randomization with no anticipated changes during the trial successfully completes baseline neuroimaging (MRI or EEG). Exclusion Criteria: • significant adverse affects that led to withdrawal or early termination from IRB 54931 or 65821. Exclusion criteria for 54931 and 65821 include: 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, or (6) the inability to drink a dissolved agent.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 13 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Acetylcysteine<br> | Drug: N-acetylcysteine<br>* 12 week administration of N-Acetylcysteine to target restricted repetitive behavior severity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glutamatergic neurometabolites (Glx) measured by proton spectroscopy Magnetic Resonance Imaging (MRI) |  | Baseline and Week 12 of treatment | 
| Change in restricted and repetitive behaviors as measured by Children's Yale Brown Obsessive Compulsive Scale - Autism Spectrum Disorder (CYBOCS-ASD) | Higher scores on the Children's Yale Brown Obsessive Compulsive Scale - Autism Spectrum Disorder mean higher levels of restricted and repetitive behaviors (Raw Score Total Range: 0-20) | Screening, Week 8, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gamma band amplitude and synchronization measured by electroencephalography (EEG) |  | Baseline, Week 12 | 
| Change in restricted repetitive behavior subtypes as measured by the Restricted Behavior Scale - Revised (RBS-R) | Higher scores on the Repetitive Behavior Scale- Revised mean higher levels of repetitive and restricted behaviors. (Raw Score Total Range: 0 - 129) | Baseline, week 8, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic Resonance Imaging, N-acetylcysteine, Restricted and Repetitive Behaviors, Electroencephalography