Omega-3 Fatty Acids + Inositol and N-acetylcysteine for Autism Spectrum Disorders

Overseen By Hannah O'Connor, BS

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Disqualifiers: Serious illness, Bleeding disorders, Seizure 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of natural treatments like omega-3 fatty acids, inositol, and N-acetylcysteine (NAC) for managing mood issues in children and teens with non-verbal learning disability (NVLD) or Autism Spectrum Disorder (ASD). Researchers aim to assess how well these treatments address emotional challenges. Participants will be divided into groups to receive either omega-3 plus inositol or NAC. Suitable candidates for this trial are children and teens aged 5-17 with NVLD or ASD who currently experience emotional outbursts or mood swings. As a Phase 4 trial, this study involves treatments already FDA-approved and proven effective, seeking to understand how they can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research has shown that omega-3 fatty acids and inositol are generally safe for children with autism spectrum disorder (ASD). A review of studies found these supplements to be well-tolerated, and their use as part of dietary treatments appears safe. Another study suggested that omega-3 fatty acids might help reduce symptoms in children with ASD.

For N-acetylcysteine (NAC), studies have shown promising safety results. NAC has been reported as safe and tolerable, helping to reduce hyperactivity and irritability in children with autism. Trials have demonstrated that NAC is generally well-tolerated without serious side effects.

Both treatments have been studied in children with ASD and appear to be safe options based on current research. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for Autism Spectrum Disorders because they bring new approaches to the table. Unlike typical medications that focus on behavioral symptoms, Omega-3 fatty acids combined with inositol and N-acetylcysteine aim to address underlying biochemical imbalances. Omega-3s and inositol are known for their potential to support brain health, while N-acetylcysteine offers antioxidant properties that can help reduce oxidative stress. This dual approach could offer a more holistic alternative to current treatments, potentially improving outcomes for those on the autism spectrum.

What evidence suggests that this trial's treatments could be effective for mood dysregulation in children and adolescents with NVLD or ASD?

This trial will compare two treatments for Autism Spectrum Disorders: Omega-3 Fatty Acids + Inositol and N-acetylcysteine (NAC). Research has shown that omega-3 fatty acids, particularly DHA and EPA, may enhance memory, attention, and decision-making skills in children with Autism Spectrum Disorder (ASD). However, a detailed review found no significant effect of omega-3 fatty acids and inositol on ASD symptoms. In contrast, N-acetylcysteine (NAC) has been found to be safe and can reduce hyperactivity and irritability while improving social awareness in children with ASD. Some studies also reported that NAC treatment led to improvements in irritability and hyperactivity. Overall, while NAC shows promise for certain behavioral symptoms, the evidence for omega-3 fatty acids and inositol remains less clear. ^{1 2 3 4 6}

Who Is on the Research Team?

Janet Wozniak, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 5-17 with non-verbal learning disability (NVLD) or Autism Spectrum Disorder (ASD), who have trouble managing their emotions. They must be able to swallow pills, understand English well enough for study requirements, and use a computer with internet for remote assessments. Exclusions include an IQ below 70, certain medical conditions, risk of suicide, pregnancy, nursing mothers, or known sensitivity to the trial supplements.

Inclusion Criteria

You have been diagnosed with non-verbal learning disability or Autism Spectrum Disorder, or have specific scores on a behavior checklist.

Subjects and their caregivers must be English-speaking and have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.

You have severe symptoms of anxiety, depression, aggression, and attention issues.

Exclusion Criteria

Your IQ is less than 70.

You weigh less than 12.5 kilograms.

You have a seizure disorder that is not under control or not being treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive omega-3 fatty acids, inositol, or N-acetylcysteine for mood dysregulation over a 6-week period

6 weeks

Conducted via telepsychiatry

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Open-label Treatment with N-acetylcysteine
• Open-label Treatment with Omega-3 Fatty Acids + Inositol

Trial Overview The study tests natural treatments: Omega-3 fatty acids plus Inositol versus N-acetylcysteine (NAC) over six weeks to see which is better at helping kids with NVLD/ASD manage mood swings. It's an open-label trial where both researchers and participants know what treatment is being given.

How Is the Trial Designed?

Group I: Omega-3 Fatty Acids + Inositol Experimental Treatment 1 Intervention

Subjects will be treated with 1020mg QAM + 1020mg QPM of omega-3 fatty acids and inositol based on weight (subjects under 25kg: 1000mg QD; Subjects weighing 25kg or more: 2000mg QD).

Group II: N-acetylcysteine Experimental Treatment 1 Intervention

Subjects will be treated with N-acetylcysteine capsules (subjects ages 5-12: 1800mg QD; subjects ages 13-17: 2400 mg QD) or effervescent tablets (subjects ages 5-12: 1800mg QD; subjects ages 13-17: 2700 mg QD) based on age.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Demarest Lloyd Jr. Foundation

Collaborator

Trials

1

Recruited

60+

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 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]

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]

In a pilot study involving 10 children aged 4-7 with autism spectrum disorder (ASD), 8 out of 9 participants who completed the study showed about a 33% improvement in autism symptoms after taking 1 gram of omega-3 fatty acids daily for 12 weeks.

The study found omega-3 fatty acids to be safe, with no reported side effects, suggesting they may be a beneficial intervention for children with ASD, although further research with larger groups is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega 3 fatty acid treatment in autism. Meiri, G., Bichovsky, Y., Belmaker, RH.[2009]

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]

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 ...

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 ... The results of this study suggest that NAC treatment does not have significant impact on the core social impairment of ASD. However, the small ...

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

Antioxidant interventions in autism spectrum disorders Treatment with NAC antioxidants showed a good trend of improvement in irritability in the ABC and symptoms of hyperactivity. The effect size was small, and ...

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

The efficiency and safety of N-acetylcysteine augmentation ... Here we report six cases of autism with severe symptoms of irritability and aggression, four of them responded to NAC treatment, while two did not. The Clinical ...

6. 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 ...