N-acetylcysteine for Autism

Overseen By Katherine Paszek, MA

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Stanford University

Disqualifiers: Significant medical problems, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a nutritional supplement called N-acetylcysteine (NAC) to help children with autism spectrum disorder. NAC has shown promise in smaller studies for reducing repetitive behaviors. The study aims to understand how NAC works and its effects on these behaviors. NAC has been studied for its potential to reduce irritability and self-injurious behaviors in children with autism spectrum disorder (ASD).

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial requires that you have been on a stable medication regimen for at least 30 days and that there are no expected changes during the trial.

What data supports the effectiveness of the drug N-acetylcysteine for autism?

Research suggests that N-acetylcysteine (NAC) may help reduce irritability and aggressive behaviors in children and adolescents with autism. In one case, a child's social interaction improved and aggressive behaviors decreased after taking NAC, indicating potential benefits for some autism symptoms. ^{1 2 3 4 5}

Is N-acetylcysteine (NAC) generally safe for human use?

N-acetylcysteine (NAC) is generally considered safe for human use and has been used for various medical purposes, including as a treatment for acetaminophen overdose and as a mucolytic agent (helps break down mucus). It is important to follow medical advice and dosage recommendations to minimize any potential side effects. ^{6 7 8 9 10}

How is the drug N-acetylcysteine unique for treating autism?

N-acetylcysteine (NAC) is unique for treating autism because it acts as an antioxidant, potentially reducing oxidative stress and neuroinflammation, which are believed to contribute to autism. Unlike other treatments, NAC may improve social interaction and decrease irritability and aggressive behaviors in individuals with autism. ^{1 3 4 5 11}

Research Team

John Hegarty, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children aged 3 to under 13 with autism spectrum disorder, confirmed by specific diagnostic tools. They must be prepubescent, medically stable, and have no metal in their body that would interfere with MRI or EEG tests. Participants should be on a steady medication and treatment plan for at least 30 days before the trial starts and not expected to change during the trial.

Inclusion Criteria

I have stable medication and treatments, and completed baseline brain scans.

Successful completion of IRB protocols 54931 or 68353

I am between 3 and 13 years old, diagnosed with autism, show moderate repetitive behaviors, am not yet in puberty, medically stable, and can safely have an MRI.

Exclusion Criteria

Significant adverse effects that led to withdrawal or early termination from IRB 54931 or 65821

I do not have severe psychiatric disorders, major medical issues, or take glutathione agents. I can drink dissolved medications, and at least one caregiver speaks and reads English well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-acetylcysteine (NAC) to target restricted and repetitive behaviors in children with autism

12 weeks

Visits at baseline, week 8, and week 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue receiving NAC to further assess long-term effects

Treatment Details

Interventions

• N-acetylcysteine

Trial Overview The study is testing N-acetylcysteine (NAC), a nutritional supplement thought to help reduce symptoms of autism, particularly restricted and repetitive behaviors. The research aims to understand how NAC works in the brain of children with autism.

Participant Groups

Group I: N-Acetylcysteine Experimental Treatment 1 Intervention

N-acetylcysteine is already approved in United States, European Union for the following indications:

Approved in United States as N-acetylcysteine for:

• Acetaminophen overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Approved in European Union as N-acetylcysteine for:

• Paracetamol overdose
• Chronic bronchitis
• Cystic fibrosis
• Mucolytic agent

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

In a 12-week study involving 31 youth with autism spectrum disorder (ASD), oral N-acetylcysteine (NAC) was well tolerated and successfully increased blood levels of glutathione, an important antioxidant.

However, NAC did not show a significant improvement in social impairment compared to placebo, indicating that while it may have some biological effects, it does not translate to clinical efficacy in treating core symptoms of ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. Wink, LK., Adams, R., Wang, Z., et al.[2018]

N-acetylcysteine (NAC) combined with risperidone significantly reduced irritability in children and adolescents with autism spectrum disorders (ASD) over an 8-week period, compared to risperidone with a placebo.

The treatment was generally well-tolerated, with only mild adverse effects reported, such as constipation and increased appetite, and no serious side effects were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. Ghanizadeh, A., Moghimi-Sarani, E.[2022]

In a 10-week clinical trial involving 40 children aged 4 to 12 with autistic disorders, N-acetylcysteine (NAC) was found to significantly reduce irritability and hyperactivity when used alongside risperidone.

The study suggests that NAC can be a beneficial adjunct therapy for managing symptoms of autistic disorders, enhancing the effectiveness of standard treatment with risperidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: a randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. Nikoo, M., Radnia, H., Farokhnia, M., et al.[2022]

A 17-year-old patient with autism spectrum disorder (ASD) showed significant reductions in irritability and aggressive behaviors after being treated with acetylcysteine, which was well tolerated and allowed for a decrease in other medications.

Acetylcysteine's effectiveness in managing ASD symptoms may be linked to its various properties, including antioxidant and anti-inflammatory effects, and it does not carry the sedative or adverse effects associated with other common treatments like atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetylcysteine for treatment of autism spectrum disorder symptoms. Stutzman, D., Dopheide, J.[2019]

A case study of a child with autism showed significant improvement in symptoms after taking oral N-acetylcysteine at a dosage of 800 mg/day for two months, with notable increases in social interaction.

The child's social impairment score decreased from 10 to 6, and aggressive behaviors dropped from 10 to 3, suggesting that N-acetylcysteine may help alleviate certain autism symptoms, potentially due to its role in reducing oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-acetylcysteine for treatment of autism, a case report. Ghanizadeh, A., Derakhshan, N.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled pilot study of N-acetylcysteine in youth with autism spectrum disorder. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A randomized double blind placebo controlled clinical trial of N-Acetylcysteine added to risperidone for treating autistic disorders. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: a randomized, double-blind, placebo-controlled clinical trial of efficacy and safety. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Acetylcysteine for treatment of autism spectrum disorder symptoms. [2019]

5. India pubmed.ncbi.nlm.nih.gov

N-acetylcysteine for treatment of autism, a case report. [2021]

6. Denmark pubmed.ncbi.nlm.nih.gov

Mycophenolates in transplantation. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Influence of renal insufficiency on pharmacokinetics of ACYL-glucuronide metabolite of mycophenolic acid in renal transplant patients. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Comparison between pre- and posttreatment clinical and renal biopsies in children receiving low dose ciclosporine-A for 2 years for steroid-dependent nephrotic syndrome. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

pH-Responsive Alginate-Based Microparticles for Colon-Targeted Delivery of Pure Cyclosporine A Crystals to Treat Ulcerative Colitis. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of cyclosporine in toxicological studies. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

The Use of N-acetylcysteine Supplementation to Decrease Irritability in Four Youths With Autism Spectrum Disorders. [2020]