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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Sleep disturbances and sensory sensitivities are common disabling features of autism, but their underlying causes are not clear. We hypothesize that both of these difficulties reflect disrupted communication between a deep brain structure, the thalamus, and the brain's outer layer, the cortex. This communication is mediated by the thalamic reticular nucleus (TRN). Due to its small size and location deep in the brain, we cannot assess TRN function without invasive techniques. Fortunately, sleep spindles, a specific brain rhythm provide a noninvasive read-out of TRN function. In Aim 1 we will examine whether reduced sleep spindles are related to worse sleep quality, impaired selective attention during wake, and sensory sensitivities in children with autism. In Aim 2, we will determine whether melatonin, which is commonly used to improve sleep, also increases sleep spindles in autism. If successful, this study will introduce TRN as a target for treatment of sleep disruption and guide larger home-based sleep studies.

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.

What data supports the effectiveness of the drug melatonin for autism?

Research shows that melatonin can help improve sleep quality in people with autism by increasing total sleep time, reducing the time it takes to fall asleep, and enhancing sleep efficiency. Additionally, prolonged-release melatonin has been shown to improve child behavior and caregiver quality of life. ^{1 2 3 4 5}

How does the drug melatonin differ from other treatments for autism?

Melatonin is unique for treating sleep problems in autism because it helps regulate the body's natural sleep-wake cycle, improving sleep onset and efficiency. Unlike other treatments, it is available in prolonged-release formulations specifically designed for children, ensuring consistent dosing and addressing long-term safety concerns. ^{1 2 5 6 7}

Research Team

Dara Manoach, PhD

Principal Investigator

Professor

Eligibility Criteria

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

12-18 years of age

English speaking

Able to understand and respond to questionnaires in English

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Melatonin for sleep disorders in people with autism: Systematic review and meta-analysis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

The melatonin receptor agonist ramelteon effectively treats insomnia and behavioral symptoms in autistic disorder. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. [2021]

7. England 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. [2022]