Melatonin for Insomnia

No longer recruiting at 1 trial location

Overseen By Diane B Boivin, MD, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Douglas Mental Health University Institute

Disqualifiers: Psychopathology, Gynecological pathology, Sleep apnea, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how melatonin affects sleep and daily rhythms in postmenopausal women with insomnia. Participants will take either a melatonin pill or a placebo (a look-alike pill with no active ingredients) before bed for 15 days. This trial suits women who struggle with falling or staying asleep, feel it impacts their daytime activities, and have been without a period for at least a year. As an unphased trial, it offers a unique opportunity to contribute to understanding how melatonin can improve sleep patterns in postmenopausal women.

Will I have to stop taking my current medications?

Yes, participants need to be drug-free at the time of the study.

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

Research shows that melatonin is generally safe. Studies, particularly those involving children, have found that a 2 mg dose of slow-release melatonin is well-tolerated. Serious side effects can occur but are rare. Common mild side effects include headaches and daytime sleepiness. These studies have not revealed any unexpected safety issues. Based on this information, melatonin appears safe for short-term use to aid sleep problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for insomnia, which often involve prescription medications like benzodiazepines or non-benzodiazepine sleep aids, melatonin is a natural hormone that helps regulate the sleep-wake cycle. This trial is examining a slow-release formulation of melatonin, which may offer a more sustained effect throughout the night, potentially improving sleep quality and duration. Researchers are excited about melatonin because, unlike many other sleep medications, it has a lower risk of dependency and fewer side effects. Additionally, as it is a natural supplement, it may be more appealing to those seeking alternative or complementary approaches to managing insomnia.

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

Research has shown that melatonin, which participants in this trial may receive, might help people sleep better and longer. Some studies have found that taking melatonin can improve sleep and enhance quality of life. For instance, one study showed that melatonin increased sleep time by about 30 minutes for some people. However, results can vary, and some studies found no major difference compared to a placebo, another treatment option in this trial. Overall, melatonin is generally considered safe and has helped some people fall asleep faster and stay asleep longer. ^{1 3 4 6 7}

Who Is on the Research Team?

Diane B Boivin, MD, PhD

Principal Investigator

Douglas Hospital Research Centre

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with insomnia, who have trouble sleeping at least three nights a week and it's been going on for over three months. They should not be heavy users of coffee, tobacco, or alcohol and must not have any psychological conditions or other medical issues that could interfere with the study.

Inclusion Criteria

You are not currently taking any medications and have only used moderate amounts of coffee, tobacco, alcohol, or other substances in the past.

I am a woman with insomnia for 3 months due to menopause.

I am a postmenopausal woman who has not had a period for at least 12 months.

Exclusion Criteria

You have worked night shifts or traveled across more than 2 time zones in the 2 months before the study.

You show signs of mental health issues during specific interviews and questionnaires.

I have not had any gynecological conditions or surgeries that could affect this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ambulatory Phase 1

Participants receive either melatonin or placebo for 15 days, taking 2 mg of exogenous melatonin in a slow release formulation (or placebo) 60 mins prior to bedtime.

2 weeks

Home-based, daily administration

Wash-out Period

Participants stop taking their melatonin/placebo pills for at least 2 weeks before switching treatments.

2 weeks

Ambulatory Phase 2

Repetition of Ambulatory Phase 1 with the opposite treatment (melatonin or placebo).

2 weeks

Home-based, daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Melatonin
• Placebo

Trial Overview

The study tests if taking melatonin (a sleep hormone) helps improve sleep in these women. It's a crossover study where participants will use either melatonin or a placebo without knowing which one they're taking first, then switch after 15 days.

How Is the Trial Designed?

Group I: Melatonin Experimental Treatment 1 Intervention

2 mg oral tablet, melatonin slow release formulation, 1x 60 min before bedtime for 15 days

Group II: Placebo Placebo Group 1 Intervention

2 mg oral tablet, 1x 60 min before bedtime for 15 days

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?

Douglas Mental Health University Institute

Lead Sponsor

Trials

31

Recruited

2,800+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

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]

Melatonin, particularly in the form of prolonged-release preparations like Circadin®, has been shown to improve sleep quality and reduce sleep latency in older adults, with a well-tolerated dosage of 2 mg once daily over 3 months.

Circadin® does not produce rebound effects or cognitive impairments commonly associated with traditional hypnotics, making it a safer first-line treatment option for insomnia in patients aged 55 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged-release formulation (Circadin®) in insomnia]. Quera-Salva, MA., Claustrat, B.[2019]

Melatonin is a hormone that helps regulate sleep-wake cycles and has been used to treat various sleep disorders, including jet lag and insomnia.

Prolonged-release melatonin (Circadin) has recently been licensed in the UK specifically for treating primary insomnia, suggesting it may be an effective option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for primary insomnia? [2017]

In a postmarketing surveillance study of 653 patients aged 55 and older, prolonged-release melatonin (PRM) significantly improved sleep quality from an average score of 4.2 to 2.6 and morning alertness from 4.0 to 2.5 over three weeks of treatment.

PRM demonstrated a low incidence of rebound insomnia (3.2% early withdrawal, 2.0% late withdrawal) and was well tolerated, with minimal adverse effects, suggesting it is a safe and effective alternative to traditional hypnotics for managing insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. Hajak, G., Lemme, K., Zisapel, N.[2021]

Circadin, a prolonged-release melatonin formulation, effectively improves sleep quality and reduces sleep latency in patients aged 55 and over with primary insomnia, showing benefits in next-day alertness and overall quality of life.

Unlike traditional sedative hypnotics, Circadin does not impair cognitive or psychomotor skills, has no risk of dependence or abuse, and has a favorable safety profile with no significant adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. Zisapel, N.[2013]

Ramelteon and agomelatine are melatonergic agonists that effectively improve sleep quality and duration in patients with insomnia and major depressive disorder, respectively, by targeting MT1 and MT2 receptors in the brain.

A slow-release formulation of melatonin, Circadin, has been shown to be effective for treating sleep disorders in the elderly, highlighting the importance of formulation in enhancing therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of melatonin agonists. Cardinali, DP., Pandi-Perumal, SR., Srinivasan, V., et al.[2019]

In a study of 13 totally blind subjects, prolonged-release melatonin (PRM) improved mean nightly sleep duration by 43 minutes compared to 16 minutes in the placebo group, suggesting it may help with sleep difficulties in this population.

PRM was well-tolerated with mild to moderate adverse events, and its beneficial effects on sleep persisted even after discontinuation, indicating potential for stabilizing the biological clock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. Roth, T., Nir, T., Zisapel, N.[2022]

Citations

1.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK605080/

Melatonin for the Treatment of Insomnia: A 2022 Update - NCBI

Some studies reported improvement in sleep and quality of life outcomes with melatonin, and some studies reported no difference between patients who received ...

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.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04233502

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

The main objective is to compare treatment effect of Slenyto® 2 mg or 5 mg to that of placebo on sleep duration (total sleep time [TST]) as assessed by the ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S0890856717316726

Efficacy and Safety of Pediatric Prolonged-Release ...

These data indicate that PedPRM (once-daily 2-mg or 5-mg dose) was effective and safe for 13 weeks of treatment in children with ASD and other ...

5.

thelancet.com

thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00225-0/fulltext

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 ...

6.

psychiatryonline.org

psychiatryonline.org/doi/10.1176/appi.pn.2017.11a6

Prolonged-Release Melatonin Improves Sleep in Children ...

PedPRM also showed a favorable safety profile with no unexpected safety issues. Adverse side effects were few, with headaches and daytime ...

7.

ncbi.nlm.nih.gov

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

Melatonin for the Treatment of Insomnia in Children ... - NCBI

The short-term safety profile of melatonin suggested that it was well-tolerated, although some severe adverse events may occur. There was a lack of long-term ...