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

Targeting the Neurobiology of Restricted and Repetitive Behaviors in Children With Autism Using N-acetylcysteine: a Single-dose Challenge Study

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.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: N-Acetylcysteine

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Robin Libove, BS; Phone Number: (650) 736-1235; Email: rlibove@stanford.edu
• Study Contact Backup: Name: Lana Kamel, BS; Phone Number: (650) 723-7845; Email: autismresearch@stanford.edu

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University School of Medicine
      • Contact: John Hegarty, PhD; Phone Number: 650-736-1235; Email: hegartyj@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• children between 3 years and 12 years 11 months at the time of consent
• diagnosis of Autism Spectrum Disorder confirmed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule-2 (ADOS-2), or Brief Observation of Symptoms of Autism (BOSA), or Childhood Autism Rating Scale- Second Edition (CARS-2).
• at least moderate Restricted and Repetitive Behaviors severity defined by a Children's Yale-Brown Obsessive Compulsive Scale for children with autism spectrum disorder score ≥ 11,
• physical development indicative of prepubescence as defined by the criteria for Tanner Stage 1,
• medically stable,
• passes MR safety screening (e.g., no metal in the body).

Exclusion Criteria:

• presence of known genetic abnormalities associated with Autism Spectrum Disorder (e.g. Fragile X),
• current or life-time diagnosis of severe psychiatric disorder (e.g., schizophrenia),
• presence of significant medical problems that would interfere with participation,
• the inability of at least one caregiver to speak/read English to a sufficient level to complete study requirements and materials,
• individuals taking antioxidant agents and glutathione prodrugs, or
• the inability/unwillingness to swallow an agent during the screening visit.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetylcysteine then Placebo	Drug: N-Acetylcysteine; N-acetylcysteine Single Dose 2700 mg taken orally
Experimental: Placebo then N-acetylcysteine	Drug: N-Acetylcysteine; N-acetylcysteine Single Dose 2700 mg taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in glutamatergic neurometabolites (Glx) measured by proton spectroscopy Magnetic Resonance Imaging (MRI)	1 hour after single dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Gamma band amplitude and synchronization measured by electroencephalography	1 hour after single dose

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): February 12, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; N-acetylcysteine; electroencephalography; Restricted and Repetitive Behaviors
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: IRB-54931; 1K99HD101702 (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 submitted 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