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Trial registered on ANZCTR


Registration number
ACTRN12619001360101
Ethics application status
Approved
Date submitted
11/09/2019
Date registered
3/10/2019
Date last updated
16/11/2023
Date data sharing statement initially provided
3/10/2019
Date results information initially provided
16/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Does melatonin improve sleep and functioning in children with Fetal Alcohol Spectrum Disorder? A comparison with placebo.
Scientific title
Assessing the effect of melatonin on sleep behaviour and executive functioning in children with Fetal Alcohol Spectrum Disorder
Secondary ID [1] 299249 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Insomnia Disorder 314384 0
Fetal Alcohol Spectrum Disorder 314385 0
Delayed Sleep-Wake Phase Disorder 314619 0
Condition category
Condition code
Mental Health 312719 312719 0 0
Other mental health disorders
Reproductive Health and Childbirth 312720 312720 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Prior to receiving medication treatments, parents/carers will also receive basic sleep hygiene information via a brief interview with a researcher (approximately 30 mins) and an information booklet to implement for four weeks. The sleep hygiene information will cover basic behavioral routine tips and environmental issues that can affect sleep quality that have been readily designed specifically for this study. If the study child's sleep is still disturbed after this period (ie over this period they still meet criteria), they will be entered into the melatonin/placebo treatment phase.

Across a 6 week cross-over trial, children will receive sublingual liquid melatonin for a three week period and a placebo for a three week period. The order of these treatment periods will be randomised per participant. Children will be prescribed a dose of 0.1 mg of melatonin per kilogram of body weight, with a maximum dose of 6 mg. Because melatonin has a short half-life, there will be no wash out period. However, analysis after the trial may exclude the first 1-3 days of data collected from participants in the placebo phase who had previously been in the melatonin phase in an effort to minimise any carry-over effects. Participants will record their melatonin use in a sleep diary. Products will also be returned and weighed at the end of the trial.
Intervention code [1] 315541 0
Treatment: Drugs
Comparator / control treatment
For another treatment phase, children will receive a placebo liquid (includes glycerin, flavouring, stevioside) that will appear and taste identical to the melatonin liquid.
Control group
Placebo

Outcomes
Primary outcome [1] 321358 0
Sleep behaviour measured using a sleep diary and actigraphy
Timepoint [1] 321358 0
Daily for 10 weeks
Secondary outcome [1] 374757 0
Parent Stress Index
Timepoint [1] 374757 0
Start of sleep hygiene phase (start of week 1), end of sleep hygiene phase/start of treatment phase 1 (start of week 5), end of treatment phase 1/start of treatment phase 2 (start of week 8), end of treatment phase 2 (start of week 11),
Secondary outcome [2] 374758 0
Child Behavioural Functioning using the BRIEF
Timepoint [2] 374758 0
Start of sleep hygiene phase (start of week 1), end of sleep hygiene phase/start of treatment phase 1 (start of week 5), end of treatment phase 1/start of treatment phase 2 (start of week 8), end of treatment phase 2 (start of week 11),
Secondary outcome [3] 375001 0
Parental stress will be measured using the Parenting Stress Index short form (PSI-SF), which is a well validated self-report measure comprising 36 items measured using a five-point Likert scale of perceived stress in the parenting role (Reitman, Currier, & Stickle, 2002). The three subscales are Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. PSI-SF scores are highly stable over a 1-year period, rs = .61-.75 (Haskett, Ahern, Ward, & Allaire, 2006) and are internally consistent, as = .74-.88 (Haskett et al., 2006). PSI-SF subscale scores map on highly to other measures of parental well-being and parent-child relationship quality (Haskett et al., 2006; Reitman et al., 2002). Parents will fill out the Parenting Stress Index short form at the end of every study phase during each scheduled visit. This assessment will be administered during each home visit from the beginning of the treatment phase.
Timepoint [3] 375001 0
Start of sleep hygiene phase (start of week 1), end of sleep hygiene phase/start of treatment phase 1 (start of week 5), end of treatment phase 1/start of treatment phase 2 (start of week 8), end of treatment phase 2 (start of week 11),
Secondary outcome [4] 416515 0
Measuring executive functioning using the Early Years Toolbox. We are proposing to use tasks from the Early Years Toolbox (EYT) to assess changes in cognition across the course of the trial. In particular, we are proposing to use the Mr Ant, Not this, Go/No-go, and Card Sorting tasks to tap into different aspects of cognitive functions that support self-regulation. Each task takes approximately 5-8 minutes to perform on an iPad and are purposefully designed to be child-friendly (see website http://www.eytoolbox.com.au). They have been normed on 1764 Australian children and demonstrated adequate psychometric properties (Howard & Melhuish, 2017). The YET measures showed moderate convergent validity with comparable assessments from the NIH toolbox, a well-established neuropsychological assessment battery (r => 0.40). Importantly, when compared with the NIH toolbox, the EYT performed better in terms less children at the floor of the assessment (2.3% vs 10.6%) and less children withdrawing from the assessment prematurely (0.9% vs 4.7%) .These are important metrics for repeated measures designs that are attempting to track change in performance over time.
Timepoint [4] 416515 0
Start of sleep hygiene phase (start of week 1), end of sleep hygiene phase/start of treatment phase 1 (start of week 5), end of treatment phase 1/start of treatment phase 2 (start of week 8), end of treatment phase 2 (start of week 11),
Secondary outcome [5] 416516 0
Executive functioning will be assessed using the NEPSY-II Inhibition. It involves asking children to look at black and white shapes and arrows on a page and to name either the shape, the direction of the arrow, or an alternative response depending on the shape, colour, and direction of the arrow. The basic premise is that children will at some point have to suppress an automatic response (e.g., seeing a black shape up and saying “black”) in favour of an effortful response (saying “white”). Their correct responses, errors, self-corrections, and response times are manually recorded by the researcher. This is a paper-based task that is normed for children from 5 to 16 years old and has been used successfully with children with FASD by the research team in a related project.
Timepoint [5] 416516 0
Start of sleep hygiene phase (start of week 1), end of sleep hygiene phase/start of treatment phase 1 (start of week 5), end of treatment phase 1/start of treatment phase 2 (start of week 8), end of treatment phase 2 (start of week 11),
Secondary outcome [6] 416517 0
Heart rate monitoring during cognitive tasks. Heart rate monitors that track heart activity using electrodes placed on the chest and stomach will be used to measure how the physiological signatures of self-regulation change across the course of the trial by extracting heart rate variability.
Timepoint [6] 416517 0
Start of sleep hygiene phase (start of week 1), end of sleep hygiene phase/start of treatment phase 1 (start of week 5), end of treatment phase 1/start of treatment phase 2 (start of week 8), end of treatment phase 2 (start of week 11),

Eligibility
Key inclusion criteria
Children aged between 5- and 12-years with confirmed prenatal alcohol exposure and who have been assessed using the Australian Guidelines for the diagnosis of FASD to have either FASD with 3 Sentinel Facial Features (SFF); FASD with < 3 SFF or “At Risk” of FASD (Bower & Elliott, 2016), and with reported sleep problems (see Inclusion Criteria).
Sleep Problem Inclusion Criteria
Children will be included in the study if their parents/caregivers report that they have problems with sleep initiation, whereby sleep onset latency is equal to or greater than 30 minutes, three nights or more a week, for equal to or more than three months.
Minimum age
5 Years
Maximum age
12 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Are not currently receiving sedative medications,
2) Who have changed place of residence or primary carers in the last three months (as this instability may be contributing to sleep problems independent from FASD).
3) Have been diagnosed with Type 1 diabetes.

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)
Numbered treatment containers will be used to conceal allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An independent researcher will generate a randomization code in Stata using block randomisation with a random variable block size of 2 or 4 both to ensure balanced groups at the end of the trial and to ensure that researchers cannot deduce the assignment of participants.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Analysis Plan
A series of two-tailed paired t-tests will be used to assess the effect of melatonin medication relative to the placebo on our sleep outcome variables.
Power Analysis
The power analysis accounted for use of crossover design. Power was set at 90%, the alpha level at 0.05, the SD of the at 9.4, and expected difference at 11.4 for sleep onset latency based on a trial in children using similar methods (https://doi.org/10.1016/j.sleep.2015.01.005).

Exploratory Analyses
In addition, analyses will be carried out to explore any relationship between improvements in child and parent functioning after the sleep intervention. This may also include the use of t-tests as well as more complex statistical models.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/03/2020
Actual
12/03/2021
Date of last participant enrolment
Anticipated
2/10/2023
Actual
8/08/2022
Date of last data collection
Anticipated
31/12/2023
Actual
5/09/2022
Sample size
Target
11
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14762 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 27995 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 303785 0
University
Name [1] 303785 0
Griffith University
Country [1] 303785 0
Australia
Funding source category [2] 312801 0
Hospital
Name [2] 312801 0
Gold Coast University Hospital
Country [2] 312801 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
176 Messines Ridge Road, Mount Gravatt, Queensland 4122, Australia
Country
Australia
Secondary sponsor category [1] 303909 0
None
Name [1] 303909 0
Address [1] 303909 0
Country [1] 303909 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304306 0
Gold Coast Hospital and Health HREC
Ethics committee address [1] 304306 0
Office for Research Governance and Development
Level 2, PED Building, E Block
Gold Coast University Hospital
1 Hospital Boulevard
Southport, QLD, 4215
Ethics committee country [1] 304306 0
Australia
Date submitted for ethics approval [1] 304306 0
11/09/2019
Approval date [1] 304306 0
17/07/2020
Ethics approval number [1] 304306 0
HREC/2019/QGC/57775

Summary
Brief summary
This proposal aims to evaluate whether liquid melatonin can be used to improve sleep in children aged 5-8 years with or at risk of FASD as per the Australian Guidelines for the Diagnosis of FASD. In addition we will investigate how any changes in child sleep behaviour owing to the intervention will lead to effects on parent wellbeing, child behavioural functioning, and child neuropsychological functioning.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96470 0
Prof Sharon Dawe
Address 96470 0
Griffith University
School of Applied Psychology
176 Messines Ridge Road, Mount Gravatt, Queensland 4122
Country 96470 0
Australia
Phone 96470 0
+61 7 3735 3371
Fax 96470 0
Email 96470 0
[email protected]
Contact person for public queries
Name 96471 0
Ned Chandler-Mather
Address 96471 0
Griffith University
School of Applied Psychology
176 Messines Ridge Road, Mount Gravatt, Queensland 4122
Country 96471 0
Australia
Phone 96471 0
+61 737355920
Fax 96471 0
Email 96471 0
[email protected]
Contact person for scientific queries
Name 96472 0
Ned Chandler-Mather
Address 96472 0
Griffith University
School of Applied Psychology
176 Messines Ridge Road, Mount Gravatt, Queensland 4122
Country 96472 0
Australia
Phone 96472 0
+61 737355920
Fax 96472 0
Email 96472 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To protect privacy of vulnerable participants.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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