Melatonin for Autism

Overseen By Dara Manoach, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Melatonin

Disqualifiers: Pregnancy, Substance abuse, Neurological disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 2 nights

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how melatonin might improve sleep and reduce sensory sensitivities in children with autism. Researchers examine how the thalamic reticular nucleus, a part of the brain, affects sleep and attention. Participants take a melatonin gummy before bedtime to determine if it can enhance sleep rhythms. Children with autism who struggle with sleep or sensory issues may be suitable, provided they have not experienced problems with melatonin previously. As an unphased trial, this study offers a unique opportunity to contribute to understanding melatonin's effects on sleep and sensory sensitivities in autism.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking melatonin or have had an adverse reaction to it in the past.

Is there any evidence suggesting that melatonin is likely to be safe for humans?

Research has shown that melatonin is generally safe for children and teenagers with autism, even if they have other conditions like ADHD. Studies have found that melatonin can help with sleep problems and usually doesn't cause major side effects. For short-term use, melatonin is mostly safe, though some people might feel a bit tired or sleepy during the day. In studies on long-term use, these side effects occurred in about 6% of cases. Overall, melatonin is considered well-tolerated for kids with autism who have trouble sleeping. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Melatonin is unique because it offers a natural and potentially less invasive alternative for managing sleep issues in individuals with autism. Unlike typical treatments that may involve prescription medications like clonidine or risperidone, melatonin is a hormone already present in the body, which helps regulate sleep-wake cycles. Researchers are excited about melatonin because it is administered in a convenient gummy form and could work quickly, with the potential to improve sleep patterns in just a couple of nights. This makes it an appealing option for those seeking simpler and potentially safer solutions to sleep disturbances associated with autism.

What evidence suggests that melatonin might be an effective treatment for autism?

Research has shown that melatonin, which participants in this trial will receive, can help children with autism who have trouble sleeping. One study found that melatonin helped these children fall asleep faster and wake up less often during the night. Another study showed that, on average, children slept almost an hour longer each night when they took melatonin. Parents noticed improvements in both sleep and daily behavior when their children used melatonin. Overall, melatonin is considered a safe option for improving sleep problems in children with autism. ^{2 6 7 8 9}

Who Is on the Research Team?

Dara Manoach, PhD

Principal Investigator

Professor

Are You a Good Fit for This Trial?

This trial is for English-speaking children aged 12-18 with Autism Spectrum Disorder who can understand and respond to questionnaires. It's not suitable for those pregnant, breastfeeding, with sleep-affecting medical conditions, severe head injuries, IQ below 70, other neurological disorders including seizures, diagnosed sleep disorders or genetic causes of ASD.

Inclusion Criteria

English speaking

Able to understand and respond to questionnaires in English

Both boys and girls with Autism Spectrum Disorder (ASD).

Exclusion Criteria

Pregnant or breastfeeding

Known genetic causes of ASD

You have long-term health conditions that make it difficult for you to sleep.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants' baseline sleep quality and sleep spindle density are assessed over five nights

2 weeks

5 nights of sleep monitoring

Treatment

Participants receive 5mg melatonin gummy 30 min before bedtime for 2 consecutive nights

2 nights

2 nights of sleep monitoring

Follow-up

Participants are monitored for changes in sleep quality and sleep spindle density after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin

Trial Overview

The study tests if melatonin improves the quality of sleep in autistic children by increasing a specific brain rhythm called 'sleep spindles'. The research aims to link better sleep and sensory processing with increased activity in a part of the brain involved in communication between its deep structures and outer layer.

How Is the Trial Designed?

Group I: Melatonin Experimental Treatment 1 Intervention

5mg melatonin gummy 30 min before bedtime for 2 consecutive nights

Melatonin is already approved in European Union, United States for the following indications:

Approved in European Union as Circadin for:

• Insomnia in adults aged 55 and over
• Sleep disorders in children with autism spectrum disorder

Approved in European Union as Slenyto for:

• Insomnia in children and adolescents aged 2-18 with autism spectrum disorder

Approved in United States as Melatonin for:

• Sleep disorders in children with autism spectrum disorder
• Insomnia in adults

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

A long-term study of a novel prolonged-release melatonin (PedPRM) showed significant improvements in sleep duration and quality for children with autism spectrum disorder and neurogenetic disorders, with 76% of participants achieving over 1 hour of improved sleep time after 39 weeks.

PedPRM was found to be generally safe, with only minor side effects like fatigue and mood swings, making it a viable long-term treatment option for insomnia in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. Maras, A., Schroder, CM., Malow, BA., et al.[2021]

Prolonged-release melatonin (Ped-PRM) has been approved as a pediatric treatment for insomnia in children and adolescents with autism spectrum disorder (ASD), showing safety for short-term use and no adverse effects on growth or development over the long term.

Melatonin is rapidly absorbed and metabolized, with immediate-release formulations being short-acting, while Ped-PRM provides sustained therapeutic levels throughout the night, highlighting the need for dose optimization due to variability in how individuals metabolize the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. Zisapel, N.[2022]

A 14-year-old boy with autism and severe mental retardation showed significant improvement in sleep patterns when melatonin was administered at 11:00 pm compared to 9:00 pm, indicating that timing of medication can influence sleep quality.

The study suggests that melatonin can effectively enhance sleep-wake rhythms in autistic individuals, as evidenced by the prolonged night sleep and reduced early morning waking during the later administration time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of melatonin on sleep-wake rhythm: the sleep diary of an autistic male. Hayashi, E.[2013]

Melatonin significantly improves sleep quality in individuals with autistic spectrum disorder (ASD), as shown by increased total sleep time, reduced sleep latency, and improved sleep efficiency based on a meta-analysis of 15 studies.

The analysis revealed a strong effect of melatonin on sleep parameters, with standardized mean differences indicating notable improvements, although wake after sleep onset and night awakenings did not show significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis. Nogueira, HA., de Castro, CT., da Silva, DCG., et al.[2023]

A study involving 26 children with autism spectrum disorder showed that immediate-release melatonin effectively improved sleep onset and sleep efficiency, indicating its potential as a treatment for sleep problems in this population.

The treatment also positively influenced circadian rhythms, as evidenced by changes in wrist skin temperature, suggesting that melatonin helps restore typical circadian patterns disrupted in autism spectrum disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels. Martinez-Cayuelas, E., Merino-Andreu, M., Losada-Del Pozo, R., et al.[2023]

In a 13-week study involving 125 children aged 2-17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome, prolonged-release melatonin mini-tablets (PedPRM) significantly improved sleep duration and onset compared to placebo.

PedPRM treatment led to notable improvements in externalizing behaviors in children and enhanced caregivers' quality of life, with 53.7% of treated subjects showing clinically relevant improvements compared to 27.6% in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life. Schroder, CM., Malow, BA., Maras, A., et al.[2020]

Ramelteon, a selective melatonin receptor agonist, showed effectiveness in improving sleep onset and maintenance in children with autism spectrum disorders (ASD), as evidenced by three case reports.

In two cases, a dose of 2 mg of ramelteon improved insomnia and behavior, while a higher dose of 8 mg was effective in the third case, suggesting that ramelteon can address both sleep and behavioral issues in patients with autistic disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The melatonin receptor agonist ramelteon effectively treats insomnia and behavioral symptoms in autistic disorder. Kawabe, K., Horiuchi, F., Oka, Y., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10166641/

Efficacy of Melatonin for Insomnia in Children with Autism ...

Conclusion Melatonin has a certain effect on relieving sleep disturbances in children with ASD, which can shorten sleep latency, reduce the number of awakenings ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0890856717316726

Efficacy and Safety of Pediatric Prolonged-Release ...

The study met the primary endpoint: after 13 weeks of double-blind treatment, participants slept on average 57.5 minutes longer at night with PedPRM compared to ...

3.

capmh.biomedcentral.com

capmh.biomedcentral.com/articles/10.1186/s13034-023-00669-w

Adherence to treatment and parents' perspective about ...

Based on parents' report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

4.

medrxiv.org

medrxiv.org/content/10.1101/2023.06.13.23291321v1

Real-life course and effectiveness of melatonin treatment ...

Results Melatonin was recommended for ∼8% of children in the ANCAN database. These children were characterized by more severe autistic ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30132686/

Long-Term Efficacy and Safety of Pediatric Prolonged ...

PedPRM was generally safe; most frequent treatment-related adverse events were fatigue (5.3%) and mood swings (3.2% of patients). Conclusion: PedPRM, an easily ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/29096777/

Efficacy and Safety of Pediatric Prolonged-Release ...

PedPRM was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without ADHD and NGD.

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35285365/

Assessing the potential for drug interactions and long term ...

Melatonin was essentially safe for short-term use (up to 3 months). Long-term data available for Ped-PRM demonstrate fatigue (6.3%), somnolence (6.3%), and ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04233502

Efficacy and Safety of Slenyto for Insomnia in Children With ...

This is a randomized placebo controlled study in children diagnosed with autism spectrum disorder (ASD), to Investigate the Efficacy and Safety of Slenyto® to ...

9.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1389945724002612

Insomnia in children affected by autism spectrum disorder

Recent data show that melatonin-based formulations are effective and safe for treating ASD-related insomnia both short and long term.