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

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a supplement called N-acetylcysteine (NAC) may reduce certain behaviors in children with autism spectrum disorder. Researchers aim to determine if NAC can lessen the severity of restricted and repetitive behaviors, common in autism. Participants will receive either NAC or a placebo for 12 weeks, allowing the study to compare the effects of the two. Suitable candidates for this trial should have autism with moderate repetitive behaviors impacting daily life and should not have other severe psychiatric disorders or significant medical problems.

As a Phase 2 and Phase 3 trial, this study measures how well NAC works in an initial group and represents the final step before FDA approval. It offers participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetylcysteine (NAC) is generally safe and well-tolerated in children with autism. Studies have found that it can reduce hyperactivity and irritability and may even improve social awareness. Its safety is well-documented, with serious side effects being rare. Most issues occur only with very high doses or unusual methods of administration. Importantly, the FDA has already approved NAC for other uses, indicating a reliable safety record. While consulting a doctor remains essential, NAC appears to be a promising option with manageable risks. ^{1 2 3 4 5}

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

N-acetylcysteine is unique because it brings a new approach to autism treatment by targeting oxidative stress and inflammation, which are believed to contribute to autism symptoms. Unlike traditional treatments such as behavioral therapy or antipsychotic medications, N-acetylcysteine works as an antioxidant that can help restore chemical balance in the brain. Researchers are excited about this treatment because it offers the potential to address underlying biochemical imbalances rather than just managing symptoms, paving the way for a more holistic approach to autism care.

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

This trial will compare N-acetylcysteine (NAC) with a placebo to evaluate its effects on autism symptoms. Research has shown that NAC may help reduce hyperactivity and irritability in children with autism and may also improve their social awareness. In other studies, NAC performed better than a placebo in reducing irritability. These findings suggest that NAC could help manage repetitive behaviors in children with autism. ^{1 3 6 7 8}

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

My child is between 3 and 12 years old.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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 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]

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/PMC4914359/

A Randomized Controlled Pilot Trial of Oral N- ... Data from this pilot investigation support the potential usefulness of NAC for treating irritability in children with autistic disorder. Large randomized ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8234027/

N-Acetylcysteine (NAC): Impacts on Human Health - PMC It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant ...

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.

8. 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 ...