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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how N-acetylcysteine (NAC), a nutritional supplement, might reduce certain behaviors in children with autism spectrum disorder. Specifically, it examines how NAC could ease restricted and repetitive behaviors, common in autism. Participants will receive either NAC or a placebo and then switch to the other group after a period of time. Children with autism who experience moderate repetitive behaviors and are medically stable may be suitable candidates for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early findings.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that N-acetylcysteine is likely to be safe for humans?

Research has shown that N-acetylcysteine (NAC) is generally safe and well-tolerated in children with autism. One study found that NAC reduced hyperactivity and irritability without causing serious side effects. Another study supported this, showing that NAC helped with irritability in children without significant negative effects. However, individuals with bleeding disorders should exercise caution, as NAC might increase the risk of bruising and bleeding. Overall, NAC appears to be a promising option with a good safety record for children with autism. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autism?

Most treatments for autism focus on behavioral and supportive therapies, sometimes combined with medications that address specific symptoms like irritability or hyperactivity, such as antipsychotics or stimulants. N-Acetylcysteine (NAC) is unique because it targets oxidative stress and glutamate regulation in the brain, offering a potential new approach to managing autism symptoms. Researchers are excited about NAC because it is an antioxidant that may reduce oxidative damage and help balance neurotransmitters, potentially leading to improvements in social behavior and communication. Unlike many current medications, which primarily manage symptoms, NAC could address underlying biological processes. This novel mechanism of action makes NAC a promising candidate for providing more comprehensive support for individuals with autism.

What evidence suggests that N-acetylcysteine might be an effective treatment for autism?

Research has shown that N-acetylcysteine (NAC) may alleviate symptoms of autism spectrum disorder (ASD). Studies have found that NAC can reduce hyperactivity and irritability in children with autism. One study showed that NAC significantly improved hyperactivity compared to a placebo. In this trial, participants will receive either NAC followed by a placebo or a placebo followed by NAC. Additionally, NAC has improved social awareness and is considered safe and well-tolerated. Overall, NAC could be a useful option for managing some autism symptoms. ^{1 2 4 6 7}

Who Is on the Research Team?

John Hegarty, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32900213/

Effectiveness of N-acetylcysteine in autism spectrum ... We concluded that N-acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03008889

A Feasibility Study of N-acetylcysteine for Self-injurious ... The purpose of this study is to demonstrate the feasibility of a 9-week, randomized trial of N-acetylcysteine (NAC) compared to placebo in 14 children (age ...

3. molecularautism.biomedcentral.com molecularautism.biomedcentral.com/articles/10.1186/s13229-016-0088-6

A randomized placebo-controlled pilot study of N ... Social impairment is a defining feature of autism spectrum disorder (ASD) with no demonstrated effective pharmacologic treatments.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584621002359

Antioxidant interventions in autism spectrum disorders Antioxidants (N-acetylcysteine (NAC), other antioxidants) are more effective than placebos in improving the irritability among symptoms in the ABC and ...

5. hub.tmu.edu.tw hub.tmu.edu.tw/en/publications/effectiveness-of-n-acetylcysteine-in-autism-spectrum-disorders-a-

Effectiveness of N-acetylcysteine in autism spectrum ... The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and ...

6. imrpress.com imrpress.com/journal/AP/21/2/10.5455/apd.53708/pdf

The efficiency and safety of N-acetylcysteine augmentation ... These data demonstrate beneficial effects with- out serious adverse effects of adding NAC to the treatment for treating irritability in children with autistic ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-1018/n-acetyl-cysteine-nac/

N-Acetyl Cysteine (Nac) – Uses, Side Effects, and More N-acetyl cysteine might increase the risk of bruising and bleeding in people with bleeding disorders. ... Autism spectrum disorder · Cardiac arrest · Cystic ...