N-Acetylcysteine for Autism

Overseen By Brianna Alconcher

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Antioxidants, Glutathione prodrugs

Disqualifiers: Genetic abnormalities, Severe psychiatric disorder, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to see if NAC, a safe nutritional supplement, can help reduce repetitive behaviors in children with autism by balancing brain chemicals. N-Acetylcysteine (NAC) has been studied for its potential benefits in treating obsessive-compulsive spectrum disorders and irritability in autism spectrum disorders.

Will I have to stop taking my current medications?

The trial requires that participants stop taking antioxidant agents and glutathione prodrugs.

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. In one case report, a child's social interaction improved and aggressive behaviors decreased after taking NAC, and other studies have explored its potential benefits when used alongside other medications. ^{1 2 3 4 5}

Is N-Acetylcysteine safe for humans?

Research on N-Acetylcysteine (NAC) for autism suggests it is generally safe for humans, as studies have focused on its safety and tolerability in children and adolescents with autism spectrum disorder. ^{1 2 3 6 7}

What makes the drug N-acetylcysteine unique for treating autism?

N-acetylcysteine (NAC) is unique for treating autism because it targets oxidative stress and neuroinflammation, which are believed to play a role in autism, and it acts as an antioxidant by providing cystine, a precursor for glutathione, an important brain antioxidant. Unlike other treatments, NAC may help improve social interaction and reduce irritability by modulating brain glutamate levels, which are often dysregulated in autism. ^{1 2 3 4 8}

Research Team

John Hegarty, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for children aged 3 to almost 13 with Autism Spectrum Disorder, confirmed by specific diagnostic tests. They must be medically stable, prepubescent, and have moderate to severe repetitive behaviors. Kids can't join if they have metal in their body (unsafe for MRI), genetic abnormalities like Fragile X, or take certain antioxidants.

Inclusion Criteria

My autism diagnosis was confirmed with specific autism assessment tools.

passes MR safety screening (e.g., no metal in the body).

I am between 3 and 12 years old.

Exclusion Criteria

I am currently taking antioxidants or glutathione supplements.

You have been diagnosed with a severe psychiatric disorder such as schizophrenia either currently or in the past.

You are not willing or able to swallow the study medication during the screening visit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of N-acetylcysteine or placebo to study its effects on restricted and repetitive behaviors in children with autism

1 day

Follow-up

Participants are monitored for safety and effectiveness after the single-dose treatment

4 weeks

Treatment Details

Interventions

• N-Acetylcysteine

Trial Overview The study is testing N-acetylcysteine (NAC), a nutritional supplement that might help reduce the severity of restricted and repetitive behaviors in autistic children. The research aims to understand how NAC affects these symptoms.

Participant Groups

Group I: Placebo then N-acetylcysteine Experimental Treatment 1 Intervention

Group II: N-acetylcysteine then Placebo Experimental Treatment 1 Intervention

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

Approved in United States as Mucomyst for:

• Mucolytic agent
• Acetaminophen overdose

Approved in European Union as Fluimucil for:

• Mucolytic agent
• Respiratory tract disorders

Approved in Canada as N-Acetylcysteine for:

• Mucolytic agent
• Acetaminophen overdose

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 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]

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]

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]

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]

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 12-week pilot study involving 33 children with autism showed that oral N-acetylcysteine (NAC) significantly reduced irritability, as measured by the Aberrant Behavior Checklist, compared to a placebo.

NAC was well tolerated with minimal side effects, suggesting it could be a safe option for managing behavioral disturbances in children with autism, warranting further large-scale studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Hardan, AY., Fung, LK., Libove, RA., et al.[2022]

A 12-week randomized controlled trial of 2,000 mg/day N-acetylcysteine (NAC) for major depressive disorder (MDD) did not show significant improvement at the primary endpoint (week 12), but indicated benefits in depressive symptoms at the post-discontinuation interview (week 16).

Qualitative analysis revealed that participants receiving NAC reported better overall depressive affect, optimism, and reduced functional impairment compared to the placebo group, suggesting that NAC may have a positive impact on individual symptoms and functional abilities despite the lack of significant results at the primary endpoint.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of N-acetylcysteine on Major Depression: Qualitative Observation and Mixed Methods Analysis of Participant Change during a 12-week Randomised Controlled Trial. Russell, SE., Skvarc, DR., Mohebbi, M., et al.[2023]

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

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

3. India pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. 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]

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

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

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

A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

The Impact of N-acetylcysteine on Major Depression: Qualitative Observation and Mixed Methods Analysis of Participant Change during a 12-week Randomised Controlled Trial. [2023]