Exogenous Melatonin in Postmenopausal Women With Insomnia

Sponsor

Douglas Mental Health University Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT05440734

Collaborator

Canadian Institutes of Health Research (CIHR) (Other)

Enrollment

Location

Arms

29.5

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Insomnia	Drug: Melatonin Drug: Placebo	N/A

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 2-week ambulatory phase at home with melatonin or placebo treatment; B) a overnight (~16-h) visit to the laboratory; C) a 2-week wash-out period; D & E) same as A & B with the opposite treatment;

Part A: The research project will start with a 14-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 2 weeks. 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: Immediately following the ambulatory phase, participants will be admitted individually to the laboratory in the early evening. They will take 2 mg of exogenous melatonin slow release (or placebo), 60 mins prior to bedtime. Participants will then sleep in the laboratory according to their habitual sleep schedule for an 8-hour nocturnal sleep period in total darkness.

Part C: 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 D & E: Repetition of Ambulatory and Laboratory phase 1 (Part A+B) except that participants who received the active treatment will now receive placebo and vice versa.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Randomized crossover placebo-controlled studyRandomized crossover placebo-controlled study

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

The nature of the treatment (melatonin vs placebo) will only be unrevealed when the key parameters have been determined (e.g, PSG sleep scoring, alertness levels, vasomotor symptoms, adverse effects, hormone levels).

Primary Purpose:

Treatment

Official Title:

Sleep and Circadian Rhythms in Men and Women - Protocol 4

Actual Study Start Date :

Jun 17, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in sleep duration [Change from baseline sleep duration at treatment day 15]
Polysomnographic sleep recordings in laboratory
Change in wake after sleep onset [Change from baseline sleep duration at treatment day 15]
Polysomnographic sleep recordings in laboratory
Change in sleep efficiency [Change from baseline sleep duration at treatment day 15]
Polysomnographic sleep recordings in laboratory
Urinary 6-sulfatoxy-melatonin levels [During sleep periods at home during the last week of treatment and during the last 2 days of each treatment phase]
Urinary samples

Secondary Outcome Measures

Change in sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) [Change between treatment conditions in PSQI score at treatment day 15]
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.
Rectal temperature [Change between treatment conditions in nocturnal levels at treatment day 15]
Core body temperature measured using a rectal probe throughout the laboratory visits
Nocturnal skin temperature [Change between treatment conditions at bedtime at treatment days 12-15]
Skin measured around the nocturnal sleep periods

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 65 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).