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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to examine how melatonin, a natural sleep hormone, affects sleep and daytime activities in teens with sleep difficulties, such as trouble falling or staying asleep. Participants will receive either melatonin or a placebo (a harmless pill resembling melatonin but with no effect) to compare results. The trial seeks teens aged 13 to 17 who have self-identified sleep issues and have never taken melatonin before. As an unphased trial, this study provides a unique opportunity for teens to contribute to understanding sleep issues and potential treatments.

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.

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

Research has shown that melatonin is generally safe for children and teens with sleep problems. One study found that using melatonin for an average of 3.7 years did not cause any serious safety issues, though some participants experienced minor side effects. Another study found melatonin effective and safe for children and teens with conditions like ADHD and autism. Most participants did not encounter major problems. Overall, melatonin is considered a safe option to help children and teens sleep better, with no major risks reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Melatonin is unique because it is a natural hormone that helps regulate the sleep-wake cycle, making it a gentler option than many standard sleep medications typically used for adolescents. Unlike sedative medications that can lead to dependency or have significant side effects, melatonin works by aligning with the body's natural rhythm to promote sleep. Researchers are excited about melatonin because it offers a promising alternative with fewer side effects and is particularly appealing for use in young people who may be more sensitive to stronger medications.

What evidence suggests that melatonin might be an effective treatment for sleep disorders in adolescents?

This trial will compare the effects of melatonin with a placebo in adolescents with sleep disorders. Studies have shown that melatonin can improve sleep in teenagers. In one study, children and teens who took melatonin slept about 57.5 minutes longer each night. Another study found that melatonin increased total sleep time by about 30 minutes and helped them fall asleep about 18 minutes faster. Research also shows that melatonin is generally safe and rarely causes adverse side effects. While melatonin isn't a cure, it can be a useful tool for managing sleep problems in young people. ^{4 6 7 8 9}

Who Is on the Research Team?

Tori Van Dyk, PhD

Principal Investigator

Loma Linda University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603669/

Melatonin for the Treatment of Insomnia in Children ... - NCBI There is some evidence of benefit of melatonin compared with placebo for the short-term treatment of insomnia in children and adolescents with neurodisabilities ...

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

Efficacy and Safety of Pediatric Prolonged-Release ... Results: 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 ...

3. bmjpaedsopen.bmj.com bmjpaedsopen.bmj.com/content/8/1/e001229

Insomnia and other sleep disorders in adolescence Average total sleep time was under 6 hours with prolonged sleep latency of over 3 hours. Sleep efficiency was low at 45%. Bloods: Full blood ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2589537023002250

Use of melatonin in children and adolescents with ... For these individuals, melatonin led to a moderate increase in total sleep time with 30 min and a moderate decrease in sleep latency with approximately 18 min, ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1389945718307561

Efficacy and safety of melatonin for sleep onset insomnia in ... Melatonin was effective in the short-term treatment of sleep onset insomnia in children and adolescents. •. Melatonin is a well-tolerated drug in children and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10968776/

Melatonin Use in Pediatrics: A Clinical Review on Indications ... Exogenous melatonin is typically used for sleep regulation in the context of insomnia either in healthy children or those with neurodevelopmental disabilities.

7. kosinmedj.org kosinmedj.org/journal/view.php?doi=10.7180/kmj.22.142

Safety issues regarding melatonin use in child and ... In conclusion, this study reported that long-term melatonin use for a mean of 3.7 years had no safety concerns regarding serious adverse effects ...

8. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00260-2/fulltext

The short-term and long-term adverse effects of melatonin ... Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased ( ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S109037982200085X

Melatonin usage in children and young adults, a registry ... Some studies have shown promising results indicating that melatonin can be effective for sleep disorders associated with ADHD and autism spectrum disorder (ASD) ...