N-acetylcysteine for Autism

Overseen By Brianna Alconcher

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Stanford University

Must not be taking: Glutathione agents

Disqualifiers: Genetic abnormalities, Severe psychiatric disorder, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests NAC, a safe nutritional supplement, to see if it can reduce repetitive behaviors in children with autism by balancing brain chemicals.

Will I have to stop taking my current medications?

The trial requires that participants have stable medication regimens for at least 30 days before starting and do not change them during the trial.

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

Research suggests that N-acetylcysteine (NAC) may help reduce some symptoms of autism, such as social impairment and irritability. A case report showed a child with autism had improved social interaction and reduced aggressive behaviors after taking NAC, and a meta-analysis of trials indicated potential benefits in managing autism symptoms. ^{1 2 3 4 5}

Is N-acetylcysteine safe for humans?

Research studies have evaluated the safety of N-acetylcysteine (NAC) in children and adolescents with autism spectrum disorder, and it has generally been found to be safe when used as an oral treatment. ^{1 2 4 5 6}

How does the drug N-acetylcysteine differ from other treatments for autism?

N-acetylcysteine (NAC) is unique because it targets oxidative stress and neuroinflammation, which are believed to play a role in autism, by providing cystine, a precursor for glutathione, an important antioxidant in the brain. Unlike other treatments, NAC may help reduce social impairment and aggressive behaviors in autism by modulating brain chemistry related to glutamate, a neurotransmitter involved in communication between nerve cells. ^{1 2 3 5 6}

Research Team

John Hegarty, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children aged 3 to almost 13 with autism, who show moderate to severe repetitive behaviors. They must be medically stable, not have metal implants (for MRI safety), and be in early physical development stages. Kids should be on steady medication and treatment plans for at least a month before the trial starts, with no changes expected during the study.

Inclusion Criteria

My child is between 3 and 12 years old.

My medications and mental health treatments have been stable for over a month.

My autism diagnosis was confirmed with standard assessments.

Exclusion Criteria

History of any adverse effects to glutathione agents/prodrugs

The inability of at least one caregiver to speak and read English to a sufficient level

Current or life-time diagnosis of severe psychiatric disorder (e.g., schizophrenia)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive N-acetylcysteine or placebo for 12 weeks in a double-blind, randomized, placebo-controlled trial

12 weeks

Regular visits (in-person) for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• N-acetylcysteine
• Placebo

Trial Overview The study tests N-acetylcysteine (NAC), a nutritional supplement against a placebo over 12 weeks to see if it can reduce restricted and repetitive behaviors in autistic children. It's double-blind, meaning neither researchers nor participants know who gets NAC or placebo, ensuring unbiased results.

Participant Groups

Group I: N-acetylcysteine Active Control 1 Intervention

12 week administration of active study compound

Group II: Placebo Placebo Group 1 Intervention

12 week administration of matched placebo

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]

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]

N-acetylcysteine supplementation for 8-12 weeks showed significant improvements in hyperactivity, irritability, and social awareness in children with autism spectrum disorder, indicating its potential efficacy as a treatment option.

The treatment was found to be safe and well-tolerated, but further research is needed to confirm these findings before making broad recommendations for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials. Lee, TM., Lee, KM., Lee, CY., et al.[2022]

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]

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. India pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials. [2022]

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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