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

Targeting the Neurobiology of Restricted and Repetitive Behaviors in Children With Autism Using N-acetylcysteine: A Randomized, Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Placebo; Drug: N acetyl cysteine

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: John Hegarty, PhD; Phone Number: (650)723-7845; Email: autismresearch@stanford.edu
• Study Contact Backup: Name: Ramy Chebbo; Phone Number: (650)723-7845; Email: autismresearch@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Department of Psychiatry and Behavioral Sciences
      • Contact: Ramy Chebbo; Phone Number: (650)723-7845; Email: autismresearch@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetylcysteine; 12 week administration of active study compound	Drug: N acetyl cysteine; N-acetylcysteine (NAC) is an over-the-counter dietary supplement that is relatively well tolerated and exhibits minimal side effects, even at high dosages. N
Placebo Comparator: Placebo; 12 week administration of matched placebo	Drug: Placebo; matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Children's Yale Brown-Obsessive Compulsive Scale for Autism Spectrum Disorder (CYBOCS-ASD) at 12 weeks	Severity of restricted and repetitive behaviors, higher scores indicate more severe behaviors	Screening and week 12
Change in Glutamatergic neurometabolites at 12 weeks	Glu and Glx measured by magnetic resonance imaging	Baseline and week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Restricted and Repetitive Behavior Scale Revised (RBS-R) at 12 weeks	Severity of restricted and repetitive behaviors, higher scores indicate more severe behaviors	Baseline and week 12
Change in Gamma band activity at 12 weeks	Electrical activity between 30-48 Hz measured by electroencephalography	Baseline and week 12

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: John Hegarty, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Electroencephalography; N-acetyl cysteine; Restricted and repetitive behaviors
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Amino Acids; Cysteine; Amino Acids, Sulfur; Acetylcysteine
• Other Study ID Numbers: IRB-68353; 4R00HD101702-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-Identified data will be shared with the National Database for Autism Research (NDAR)
• IPD Sharing Time Frame: The data will be shared on January 15th and July 15th each year
• IPD Sharing Access Criteria: Researchers with access to the National Database for Autism Research (NDAR) will be able to obtain the submitted data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No