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Trial registered on ANZCTR


Registration number
ACTRN12612000425897
Ethics application status
Approved
Date submitted
12/04/2012
Date registered
16/04/2012
Date last updated
22/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised Controlled Trial of Melatonin for Delayed Sleep Phase Disorder
Scientific title
The effect of melatonin on sleep onset time, sleep efficiency in the first third of the sleep episode, and sleep-related daytime impairments in people with delayed sleep phase disorder: a randomised controlled trial
Secondary ID [1] 280310 0
NIL
Universal Trial Number (UTN)
U1111-1129-9240
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
delayed sleep phase disorder 286268 0
Condition category
Condition code
Public Health 286489 286489 0 0
Other public health
Metabolic and Endocrine 286528 286528 0 0
Other metabolic disorders
Mental Health 286529 286529 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Melatonin (0.5mg) will be adminstered via oral tablet day 1 hour prior to bedtime for a minimum of 5 nights per week for a duration of 4 weeks.
Intervention code [1] 284660 0
Treatment: Drugs
Intervention code [2] 284661 0
Diagnosis / Prognosis
Comparator / control treatment
participants will receive melatonin placebo capsules (same in appearance as treatment) and be instructed to take them 1 hour prior to their desired bedtime, for the 4 weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 286932 0
Compared to placebo, melatonin treatment will result in objectively recorded earlier sleep times. Sleep related impairments will be assessed using the Patient-Reported Outcomes Measurement Information System. Also Actiwatches will be worn by participants to record sleep-wake behaviour.
Timepoint [1] 286932 0
Sleeps times will be recorded prior and during melatonin treatment. This will be for a period of approximately 4-6 weeks and will be compared.
Primary outcome [2] 286961 0
Compared to placebo, melatonin treatment will result in objectively recorded improved sleep efficiency in the first third of the sleep episode. Sleep related impairments will be assessed using the Patient-Reported Outcomes Measurement Information System. Also Actiwatches will be worn by participants to record sleep-wake behaviour.
Timepoint [2] 286961 0
Sleep efficiency will be recorded prior and during melatonin treatment. This will be for a period of approximately 4-6 weeks and will be compared.
Primary outcome [3] 286962 0
Compared to placebo, melatonin treatment will result in reduced subjective sleep-related daytime impairments assessed by the Patient-Reported Outcomes Measurement Information System. Also Actiwatches will be worn by participants to record sleep-wake behaviour.
Timepoint [3] 286962 0
Day time impairments will be recorded prior and during melatonin treatment. This will be for a period of approximately 4-6 weeks and will be compared.
Secondary outcome [1] 297013 0
Some people will be genetically pre-disposed to have a
larger melatonin treatment response.
Timepoint [1] 297013 0
DNA will be extracted from saliva samples and tested for PER3 4 and 5 repeat allelle gene, a gene linked with delayed sleep phase disorder. This will be tested prior to randomisation and correlated to melatonin treatment.
Secondary outcome [2] 316678 0
Compared to placebo, melatonin treatment will result in subjectively reduced sleep disturbances and daytime sleepiness. Validated questionnaires (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale) will be completed at baseline and post- treatment and be compared.
Timepoint [2] 316678 0
baseline and 4 weeks from intervention start date (end of melatonin treatment period).
Secondary outcome [3] 316679 0
Compared to placebo, melatonin treatment will result in a greater proportion of change in the Clinical Global Impression Scale.
Timepoint [3] 316679 0
At Baseline and 4 weeks from intervention start date (end of melatonin treatment period), a Sleep physician will complete a Clinical Global Impression Scale. The Sleep physician will remain consistent between these visits.
Secondary outcome [4] 316680 0
Compared to placebo, melatonin treatment will induce an advance in circadian phase. This will be assessed in a subset of participants who collected saliva baseline and 4 weeks from intervention start date (end of melatonin treatment period). Endogenous melatonin will be assessed in saliva samples.
Timepoint [4] 316680 0
Baseline and 4 weeks from intervention start date (end of melatonin treatment period).

Eligibility
Key inclusion criteria
1) Aged 16 to 65 years (equal gender)
2) Body mass index >18 and < 30kg/m2
3)High risk of DSPD according to established criteria (scoring online or written survey) on the DSPD screening questionnaire
4) Five or more consecutive days each week in which the individual participates in day work or school
5) Self-reported willingness to go to bed at the desired bedtime (as determined by participants)
6) Able to abstain from tobacco and alcohol for the entire trial and caffeine late in the day.
Minimum age
16 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Comorbid sleep disorder (except insomnia)
2) Drugs of abuse or concurrent medication (including OTC medicines or herbal substances) likely to affect sleep (other than antidepressants)
3) History of psychiatric disorder in the past 12 months, other than depression
4) Caffeine consumption > 300mg per day
5) Alcohol consumption > 14 standard drinks per week
6) History of substance in the past 12 months
7) Investigational drug use in the past 60 days
8) Pregnancy or lactation
9) Night shift work in the past 6 months
10) Transmeridian travel in the past 2 months
11) Allergies to any medicines, foods, preservatives or dyes
12) Liver, kidney, or autoimmune disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Following written informed consent, screening procedures (including confirmation of the DSPD diagnosis),
and provision of an oral swab for genetic analysis (visit 1), participants will complete one week of sleep-wake
monitoring (at home). At visit 2, the timing of the nightly rise in melatonin production will be assessed in
saliva collected hourly in the 5 hours prior to and 2 hours after bedtime. Those identified as having an onset
of melatonin production (dim light melatonin onset; DLMO) at or after the subjects’ desired bedtimes will be
randomised into the trial. At visit 3, participants will receive melatonin (0.5mg) or placebo capsules and be
instructed to take them 1h prior to their desired bedtime, for the following 4 weeks. A clinical assessment of
the outcome will be conducted at visit 4. For the duration of the protocol, sleep-wake patterns and
sleep-related impairments will be recorded using an electronic wrist monitor and diary/questionnaire
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomly assigned to permuted block randomization to either melatonin or placebo in a 1:1 ratio. An externally appointed biostatistical consultant will be responsible for randomization procedures.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
N/A
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2012
Actual
13/09/2012
Date of last participant enrolment
Anticipated
30/03/2014
Actual
1/09/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
Final
104
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment postcode(s) [1] 5231 0
3000
Recruitment postcode(s) [2] 5232 0
5000
Recruitment postcode(s) [3] 5233 0
2050
Recruitment outside Australia
Country [1] 4253 0
United States of America
State/province [1] 4253 0

Funding & Sponsors
Funding source category [1] 285080 0
Government body
Name [1] 285080 0
NHMRC
Country [1] 285080 0
Australia
Primary sponsor type
Individual
Name
A/Prof Shantha Rajaratnam
Address
School of Psychlogy and
Psychiatry
Building 17
Monash University
Wellington Road
Clayton VIC 3800
Country
Australia
Secondary sponsor category [1] 283943 0
Individual
Name [1] 283943 0
Prof Leon Lack
Address [1] 283943 0
School of Psychology
Flinders University
GPO Box 2100
Adelaide SA 5001
Country [1] 283943 0
Australia
Secondary sponsor category [2] 283944 0
Individual
Name [2] 283944 0
Prof Ron Grunstein
Address [2] 283944 0
NHMRC Centre for Sleep Health
Woolcock Institute of Medical Research
PO Box M77
Missenden Road
NSW 2050
Country [2] 283944 0
Australia
Secondary sponsor category [3] 283945 0
Individual
Name [3] 283945 0
Prof David Kennaway
Address [3] 283945 0
The University of Adelaide
Medical School, North Wing
Frome Road
Adelaide SA 5005
Country [3] 283945 0
Australia
Secondary sponsor category [4] 283946 0
Individual
Name [4] 283946 0
A/Prof Steven Lockley
Address [4] 283946 0
Division of Sleep Medicine
Brigham and Women's Hospital
Harvard Medical School
221 Longwood Avenue, Suite 438
Boston MA 02115
USA
Country [4] 283946 0
United States of America
Other collaborator category [1] 260724 0
Individual
Name [1] 260724 0
Dr Tracey Sletten
Address [1] 260724 0
School of Psychology and Psychiatry
Building 17
Monash University
Wellington Road
Clayton VIC 3800
Country [1] 260724 0
Australia
Other collaborator category [2] 260725 0
Individual
Name [2] 260725 0
Dr Helen Wright
Address [2] 260725 0
School of Psychology
Flinders University
GPO Box 2100
Adelaide SA 5001
Country [2] 260725 0
Australia
Other collaborator category [3] 260726 0
Individual
Name [3] 260726 0
A/Prof Delwyn Bartlett
Address [3] 260726 0
Woolcock Institute of Medical Research
431 Glebe Point Road
Glebe NSW 2037
Country [3] 260726 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287094 0
Monash University Research Ethics
Ethics committee address [1] 287094 0
Ethics committee country [1] 287094 0
Australia
Date submitted for ethics approval [1] 287094 0
Approval date [1] 287094 0
02/04/2012
Ethics approval number [1] 287094 0
CF12/0243 - 2012000096

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34052 0
Prof Shantha Rajaratnam
Address 34052 0
School of Psychological Sciences
18 Innovation Walk (Building 17), Room 550
Monash University Clayton Campus, Wellington Road, Clayton VIC 3800
Australia
Country 34052 0
Australia
Phone 34052 0
+61 3 9905 3934
Fax 34052 0
Email 34052 0
shantha.rajaratnam@monash.edu
Contact person for public queries
Name 17299 0
Dr Michelle Magee
Address 17299 0
Sleep and Circadian Medicine Laboratory
School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences
Monash University
Be Active Sleep Eat Facility
Ground floor, 264 Ferntree Gully Road, Room G13
Notting Hill VIC, 3168
Country 17299 0
Australia
Phone 17299 0
+61 3 9905 3952
Fax 17299 0
+61 3 9905 3948
Email 17299 0
michelle.magee@monash.edu
Contact person for scientific queries
Name 8227 0
Shantha Rajaratnam
Address 8227 0
School of Psychological Sciences
18 Innovation Walk (Building 17), Room 550
Monash University Clayton Campus, Wellington Road, Clayton VIC 3800
Australia
Country 8227 0
Australia
Phone 8227 0
+61 3 9905 3934
Fax 8227 0
+61 3 9905 3948
Email 8227 0
shantha.rajaratnam@monash.edu

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEfficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial.2018https://dx.doi.org/10.1371/journal.pmed.1002587
EmbaseA PERIOD3 variable number tandem repeat polymorphism modulates melatonin treatment response in delayed sleep-wake phase disorder.2020https://dx.doi.org/10.1111/jpi.12684
N.B. These documents automatically identified may not have been verified by the study sponsor.