Exogenous Melatonin in Postmenopausal Women with Insomnia

Sleep and Circadian Rhythms in Men and Women - Protocol 4

The aim of the study is to assess the effect of exogenous melatonin, 2 mg SR, 60 minutes before bedtime for 15 days, on the sleep and circadian rhythms of postmenopausal women with insomnia in a randomized crossover placebo-controlled study.

Study Overview

• Status: Terminated
• Conditions: Insomnia
• Intervention / Treatment: Drug: Melatonin; Drug: Placebo

Detailed Description

Eligible participants will be contacted by the research team to provide informed consent for the study. Once the screening phase is completed, they will be ready to start the study consisting of:

A) a ~2-week ambulatory phase at home with melatonin or placebo treatment; B) a 2-week wash-out period; C) same as A with the opposite treatment;

Part A: The research project will start with a 16-day ambulatory data-collection period during which participants will receive either melatonin or a placebo. They will take 2 mg of exogenous melatonin in a slow release formulation (or placebo), 60 mins prior to bedtime for 15 days. Participants will be instructed to go to bed at a regular time and stay in darkness for 8 consecutive hours each night, trying to sleep.

Part B: Throughout this period, all participants will stop taking their melatonin/placebo pills. After at least 2 weeks, they will prepare to participate to the other study condition.

Parts C: Repetition of Ambulatory phase 1 (Part A) except that participants who received the active treatment will now receive placebo and vice versa.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, J4J5L8
      • Centre for Study and Treatment of Circadian Rhythms

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Insomniac women will meet the diagnostic criteria for persistent insomnia as described in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). They will report subjective sleep onset and/or maintenance difficulties associated with impaired daytime functioning at least 3 times a week, for at least 3 months. Sleep disturbances will be coincident with the onset of the menopausal transition.
• Postmenopausal women will have amenorrhea for at least 12 months.
• Participants will be drug-free at the time of study, and will have a history of only moderate or no use of coffee (≤3 cups/day), tobacco (≤ 10 cigarettes/day), alcohol (≤ 15 drinks/week), or other compounds.

Exclusion Criteria:

• Evidence of psychopathology on the Structured Clinical Interview for DSM-5, the Seasonal Pattern Assessment Questionnaire, the Beck Depression Inventory, and the Spielberger State Trait Anxiety Inventory.
• A history of prior gynecological pathology or medical condition that can affect the study results, including bilateral oophorectomy or endocrinopathy, and will not have used investigational drugs within 4 weeks of the study.
• A history of night work or transmeridian travel (across >2 time zones) in the 2 months prior to the study.
• Evidence of sleep apnea (apnea/hypopnea index > 15 per hour of sleep) or restless legs, or periodic limb movements during sleep (number of PLMs >15 per hour of sleep).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin; 2 mg oral tablet, melatonin slow release formulation, 1x 60 min before bedtime for 15 days	Drug: Melatonin; 2 Mg Oral Tablet, slow release
Placebo Comparator: Placebo; 2 mg oral tablet, 1x 60 min before bedtime for 15 days	Drug: Placebo; placebo pill identical to the treatment pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sleep duration	Sleep recorded with a portable device	Change from baseline sleep duration at treatment day 15
Change in wake after sleep onset	Sleep recorded with a portable device	Change from baseline sleep duration at treatment day 15
Change in sleep efficiency	Sleep recorded with a portable device	Change from baseline sleep duration at treatment day 15
Urinary 6-sulfatoxy-melatonin levels	Urinary samples	During sleep periods during the last 3 days of each treatment phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI)	A self-rated 19-item questionnaire, each of which has a range of 0 (no difficulty) to 3 (severe difficulty) points.These 19 items are combined to form 7 component scores reflecting different aspects of sleep quality. The 7 component scores are then added to yield one global score, with a range of 0-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all area.	Change between treatment conditions in PSQI score at treatment day 15
Nocturnal skin temperature	Skin measured around the nocturnal sleep periods	Change between treatment conditions at bedtime at treatment days 14-15

Collaborators and Investigators

• Sponsor: Douglas Mental Health University Institute
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Diane B Boivin, MD, PhD, Douglas Hospital Research Centre

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2022
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (Actual): July 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: sleep; melatonin; menopause; aging; alertness; circadian rhythms
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antioxidants; Protective Agents; Melatonin
• Other Study ID Numbers: 2018-175

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No