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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how N-acetylcysteine (NAC), a supplement, can help reduce specific behaviors in children with autism. Researchers focus on restricted and repetitive behaviors, common in autism, to determine if NAC can make a positive difference. Children on a stable medication routine who have participated in related NAC studies might be a good fit for this trial. As a Phase 2 trial, this research measures how well NAC works in an initial, smaller group of children, offering a chance to contribute to important findings.

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.

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

Research has shown that N-acetylcysteine (NAC) is safe and well-tolerated for children with autism. Studies have found that NAC can reduce hyperactivity and irritability while improving social awareness without serious side effects. One study found that adding NAC to treatment did not cause any major negative effects. The FDA has already approved NAC for other uses, indicating its safety. Overall, NAC is considered a well-tolerated option for managing symptoms in 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 managing symptoms with behavioral therapies or medications like antipsychotics. But N-acetylcysteine (NAC) offers something different. It's an antioxidant that can reduce oxidative stress and inflammation, which are believed to play a role in autism. Researchers are excited about NAC because it targets these underlying biological processes, potentially offering a new way to alleviate symptoms and improve quality of life for those with autism.

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

Research shows that N-acetylcysteine (NAC), which participants in this trial will receive, might help children with autism. Studies have found that NAC can lower hyperactivity and irritability and might also boost social awareness. Some research suggests that NAC could reduce self-harming behaviors and repetitive actions, common in autism. NAC is considered safe and well-tolerated for children. Although more research is needed, these findings suggest NAC might effectively manage certain autism symptoms. ^{1 2 5 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7025748/

The Use of N-acetylcysteine Supplementation to Decrease ... Recent studies have suggested that NAC may improve irritability, self-injurious behaviors, stereotypic and repetitive behavior, and hyperactivity in youth with ...

4. 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.

5. 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 ...

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 (NAC) comes from the amino acid L-cysteine. Amino acids are building blocks of proteins. NAC has many uses and is an FDA approved drug.