Melatonin for Sleep Disorders in Adolescents

(MARS Trial)

Recruiting at 1 trial location

Overseen By Brooke Iwamoto

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Loma Linda University

Must not be taking: Psychiatric medications, Sleep supplements

Disqualifiers: Obesity, Head injury, Caffeine, others

Compensation: Varies

Number of Visits: Unknown

Duration: 12 days

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The present study will use a within-person, randomized cross-over experimental design to test the effects of exogenous melatonin supplementation on the sleep and daytime functioning of typically developing adolescents with short or disrupted sleep of behavioral origins (i.e., difficulty falling asleep, staying asleep, or premature waking resulting in short or disrupted sleep not attributed to an organic sleep condition).

Will I have to stop taking my current medications?

The trial requires that participants do not use psychiatric medications or any drugs or supplements known to affect sleep.

What data supports the effectiveness of the drug melatonin for sleep disorders in adolescents?

Research shows that melatonin can help adolescents fall asleep faster and increase total sleep time, especially in those with sleep-onset insomnia or delayed sleep phase disorder. It is generally well-tolerated and has been found effective in both short-term and long-term use. ^{1 2 3 4 5}

Is melatonin safe for adolescents with sleep disorders?

Research shows that melatonin is generally safe and well-tolerated in children and adolescents, with no significant differences in side effects compared to a placebo. It has been used safely in doses ranging from 2-10 mg/day for sleep problems in this age group. ^{3 4 5 6 7}

How is melatonin different from other drugs for sleep disorders in adolescents?

Melatonin is unique because it is a hormone naturally produced by the body and is available over the counter, making it a more accessible option for treating sleep disorders in adolescents. It has been shown to improve sleep duration and onset without significant adverse effects, unlike some other sleep medications that may have more side effects or require a prescription. ^{3 4 5 7 8}

Research Team

Tori Van Dyk, PhD

Principal Investigator

Loma Linda University

Eligibility Criteria

This study is for typically developing teens aged 13-17 who have trouble sleeping, like difficulty falling or staying asleep, or waking up too early. They must be new to using melatonin and able to read and write in English. Teens drinking more than one caffeinated drink daily, at risk of sleep disorders (like apnea), obese, on psychiatric meds, taking sleep-affecting drugs/supplements, or with a serious head injury can't join.

Inclusion Criteria

Able to understand, read, and write in English

I have never taken melatonin.

I have trouble falling or staying asleep, leading to poor sleep.

Exclusion Criteria

You have had a head injury or concussion with loss of consciousness for more than 1 minute.

I am considered obese.

I am not taking any medications or supplements that affect my sleep.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants undergo a 2-day run-in period to establish baseline measurements

2 days

Treatment

Participants receive either melatonin or placebo for 12 days in a randomized cross-over design

12 days

Follow-up

Participants are monitored for changes in sleep and emotion regulation after treatment

2 weeks

Treatment Details

Interventions

• Melatonin
• Placebo

Trial Overview The trial is testing if melatonin supplements help improve sleep and daytime functioning in adolescents with self-reported sleep issues. Participants will receive either the melatonin supplement or a placebo without knowing which one they are taking during different periods of the study.

Participant Groups

Group I: Administration of Melatonin Experimental Treatment 1 Intervention

Group II: Administration of Placebo Placebo Group 1 Intervention

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?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Findings from Research

A small daily dose of melatonin (1 mg) taken in the afternoon significantly advanced sleep-onset times for adolescents, with students falling asleep 68 minutes earlier and sleeping 62 minutes longer compared to baseline after treatment.

The study, involving 21 students aged 14-19 over 5 weeks, showed that melatonin not only improved sleep timing but also reduced daytime sleepiness and increased evening sleepiness, suggesting it can help teenagers feel more alert during school despite irregular sleep patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin treatment effects on adolescent students' sleep timing and sleepiness in a placebo-controlled crossover study. Eckerberg, B., Lowden, A., Nagai, R., et al.[2022]

Exogenous melatonin has been shown to be effective in treating various sleep disorders, including insomnia and circadian rhythm disorders, in both children and adults, as supported by recent meta-analyses.

Despite its efficacy, melatonin is often prescribed due to its perceived low side-effect profile and cost, even in cases where high-quality evidence is lacking, and the long-term effects of melatonin use are still not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and misuse of exogenous melatonin in the treatment of sleep disorders. Riha, RL.[2019]

Melatonin significantly improved sleep onset latency and total sleep time in children and adolescents with neurodevelopmental disorders, based on a systematic review of 34 randomized control trials involving 1,998 participants.

In adults with delayed sleep phase disorder, melatonin also effectively reduced sleep onset latency and increased total sleep time, with no significant differences in tolerability compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders: A systematic review and meta-analysis. Salanitro, M., Wrigley, T., Ghabra, H., et al.[2022]

Melatonin significantly reduced sleep onset time (SOT) by an average of 0.62 hours and improved dim light melatonin onset (DLMO) by 0.82 hours in children and adolescents with sleep onset insomnia, based on a review of seven trials involving 387 participants.

The treatment was found to be effective and generally well-tolerated, with no significant differences in dropout rates due to adverse events, although some mild adverse effects were reported, indicating a need for further research, especially in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. Wei, S., Smits, MG., Tang, X., et al.[2022]

A follow-up study of 44 children with neurodevelopmental disabilities showed that long-term melatonin therapy was well-tolerated, with no adverse reactions or development of tolerance reported over a period of up to 3.8 years.

Caregivers noted significant improvements in sleep quality, which correlated with better health, behavior, and learning outcomes, suggesting that melatonin can be an effective treatment for children with treatment-resistant circadian rhythm sleep disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. Carr, R., Wasdell, MB., Hamilton, D., et al.[2013]

In a 12-week trial involving 146 children with neurodevelopmental disorders, melatonin significantly reduced the time it took for children to fall asleep by an average of 37.5 minutes, while also increasing total sleep time by about 22.4 minutes according to parent-reported diaries.

While melatonin improved sleep onset, it resulted in earlier waking times and did not lead to significant improvements in child behavior or family functioning, indicating that while it is safe and tolerable, its overall impact on sleep quality may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. Gringras, P., Gamble, C., Jones, AP., et al.[2022]

A systematic review of six randomized clinical trials involving children aged 2 to 18 with autism spectrum disorder (ASD) and/or attention-deficit hyperactivity disorder (ADHD) found that melatonin significantly improved sleep duration and reduced sleep onset latency compared to placebo.

Melatonin is considered safe and well-tolerated in children and adolescents at doses ranging from 2 to 10 mg per day, making it a viable option for treating sleep problems in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspective on Melatonin Use for Sleep Problems in Autism and Attention-Deficit Hyperactivity Disorder: A Systematic Review of Randomized Clinical Trials. Parvataneni, T., Srinivas, S., Shah, K., et al.[2020]

Sleep disorders are prevalent in Danish children and adolescents, especially those with neurodevelopmental disabilities, highlighting the need for effective treatment strategies.

The review suggests a three-stage treatment approach: improving sleep hygiene, testing weighted blankets, and using melatonin as a short-term, off-label option, given its limited approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sleep disorders in children and adolescents]. Agersted, ABA., Pagsberg, AK.[2021]

References

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

Melatonin treatment effects on adolescent students' sleep timing and sleepiness in a placebo-controlled crossover study. [2022]

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

The use and misuse of exogenous melatonin in the treatment of sleep disorders. [2019]

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

Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders: A systematic review and meta-analysis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. [2022]

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

Perspective on Melatonin Use for Sleep Problems in Autism and Attention-Deficit Hyperactivity Disorder: A Systematic Review of Randomized Clinical Trials. [2020]

8. Denmark pubmed.ncbi.nlm.nih.gov

[Sleep disorders in children and adolescents]. [2021]