Condition category
Urological and Genital Diseases
Date applied
06/12/2010
Date assigned
07/02/2011
Last edited
29/03/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Diane Boivin

ORCID ID

Contact details

6875 LaSalle Boulevard
Pavilion FBC-1
Montreal
H4H 1R3
Canada
+1 514 761 6131 ext 2397
diane.boivin@douglas.mcgill.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MOP-38064

Study information

Scientific title

Sleep and melatonin across the menstrual cycle in women with premenstrual dysphoric disorder (PMDD)

Acronym

Study hypothesis

1. The changes in sleep organization, sleep electroencephalographic (EEG) activity, core body temperature and plasma melatonin are significant across the menstrual cycle.
2. The changes in sleep organization, sleep EEG, core body temperature and plasma melatonin across the menstrual cycle are different in women with premenstrual dysphoric disorder (PMDD) when compared to healthy controls.
3. Exogenous melatonin can significantly improve sleep quality and EEG in women with PMDD during the premenstrual period of their menstrual cycle.

Ethics approval

Douglas Mental Health University Institute Research Ethics Board approved on the 8th December 1998 (ref: REB 98-29)

Study design

Single centre open-label intervention study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Premenstrual dysphoric disorder (PMDD)

Intervention

PMDD participants were given a 2 mg tablet of slow-release melatonin taken orally 60 minutes prior to bedtime. Melatonin was administered each night during the luteal phase of the menstrual cycle for three consecutive menstrual cycles. The treatment began three days after the projected time of ovulation and ended on the first day of the subsequent menstrual period (menses onset). This was an open-label study comparing the effect of the treatment phase with the baseline no-intervention phase which occurred during the menstrual cycle before the three months of treatment. Total duration of treatment was for three consecutive months during which exogenous melatonin was administered selectively during the luteal phase (i.e. approximately the last two weeks of the menstrual cycle).

Intervention type

Drug

Phase

Not Applicable

Drug names

Melatonin

Primary outcome measures

The experimental protocol consisted of two phases, including a baseline and intervention condition. Each phase consisted of a menstrual cycle during which data were collected. The intervention lasted three menstrual cycles with the last menstrual cycle consisting of a repeat of the data collected during baseline. During each menstrual cycle of data collection, participants entered the laboratory every third night and had two 24-hour periods of investigation at the follicular and luteal phases of their menstrual cycle. Core body temperature was measured continuously via rectal sensor throughout all nocturnal laboratory visits throughout the menstrual cycle (~ 8 - 10 visits) at baseline and treatment phases, and also during the two separate 24-hour visits planned to occur in the follicular phase and the luteal phase of the menstrual cycle in both baseline and treatment phases. Polysomnographic sleep was recorded during each nocturnal laboratory visit throughout the menstrual cycle (~ 8 - 10 visits) at baseline and treatment phases. In addition, urine samples were collected during nocturnal visits before and after the sleep episode and 1x/3 hours throughout the 24-hour visits to measure their content in 6-sulfatoxy-melatonin. Saliva samples were also collected 2x/hour at nocturnal visits and throughout the waking episode across the 24-hour laboratory visits. Plasma melatonin was sampled via indwelling forearm catheter throughout each of the two separate 24-hour laboratory visits, planned to occur during the follicular phase and the luteal phase of the menstrual cycle in both baseline and treatment phases.

Secondary outcome measures

All participants filled out a post-sleep questionnaire each day throughout the experiment, which assessed subjective sleep quality via a 7-point Likert Scale, subjective sleep onset latency, subjective sleep duration, morning anxiety levels via visual analogue scale (VAS; 100-mm bipolar scale, with 0 mm being "extremely calm" and 100 mm being "extremely agitated") and a summary of dream content. All participants also filled out an 11-item VAS (100-mm bipolar scale, with 0 mm being "not at all" and 100 mm being "extreme symptoms") for mood and symptom assessments which included the measures depressed mood, tension, affective lability, irritability, decreased interest, difficulty concentrating, lack of energy, change in appetite, change in sleep patterns, feeling out of control, and physical symptoms. While in the laboratory, subjective alertness (100 mm bipolar VAS administered every 20 minutes; 0: "extremely sleepy", 100: "extremely alert"), subjective mood (100 mm bipolar VAS administered every 20 minutes; 0: "extremely happy", 100: "extremely sad"), subjective excitedness (100 mm bipolar VAS administered every 20 minutes; 0: "extremely calm", 100: "extremely excited") and cognitive performance (4-minute calculation test administered every 60 minutes) were also assessed. Distal skin temperature at the hands and feet was recorded 1x/min throughout all laboratory visits in four control participants, two PMDD participants during the baseline phase, and one PMDD participant during the treatment phase. Peripheral blood mononuclear cells were collected 1x/2 hours in one control participant across both 24-hour laboratory visits.

Overall trial start date

20/01/2001

Overall trial end date

31/12/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Patients:
1. Females aged between 18 and 45 years old
2. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) research criteria for clinical diagnosis of PMDD. This was determined by meeting with a trained psychiatrist during the asymptomatic follicular phase and the symptomatic late luteal phase.
3. Required to fill out an 11-item visual analogue scale (VAS) for at least two consecutive menstrual cycles. The 11-item VAS (10-mm bipolar scale, with 0 mm being "not at all" and 100 mm being "extreme symptoms") was based on the DSM-IV criteria for PMDD diagnoses and included the measures depressed mood, tension, affective lability, irritability, decreased interest, difficulty concentrating, lack of energy, change in appetite, change in sleep patterns, feeling out of control, and physical symptoms. An individual mean score for each of the four core PMDD symptoms (depressed mood, tension, affective lability and irritability) was calculated for days 6 - 10 after menstruation and also for the last 5 days of the menstrual cycle (late luteal phase). Eligibility criteria required an increase of at least 200% on one, or at least 100% on two or more of the core symptoms for the mean late luteal phase score compared to the follicular phase.

Age-matched controls:
4. Completed the VAS during screening and who showed no evidence of PMDD or any other psychiatric disorder

Both groups:
5. All participants had a history of regular menstrual cycles (range: 25-34 +/- 3 days)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

9 women diagnosed with PMDD and 9 age-matched controls (total = 18)

Participant exclusion criteria

1. Diagnosed with seasonal affective disorder (SAD) or any other Axis I or II disorder
2. Drug use
3. Oral contraceptives
4. History of gynecological pathology
5. History of night-shift work or transmeridian travel within three months prior to study

Recruitment start date

20/01/2001

Recruitment end date

31/12/2012

Locations

Countries of recruitment

Canada

Trial participating centre

6875 LaSalle Boulevard
Montreal
H4H 1R3
Canada

Sponsor information

Organisation

Douglas Mental Health University Institute (Canada)

Sponsor details

6875 LaSalle Boulevard
Montreal
Quebec
H4H 1R3
Canada
+1 514 761 6131
diane.boivin@douglas.mcgill.ca

Sponsor type

University/education

Website

http://www.douglas.qc.ca/

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MOP-38064)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes