Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000017527p
Ethics application status
Submitted, not yet approved
Date submitted
25/10/2023
Date registered
10/01/2024
Date last updated
10/01/2024
Date data sharing statement initially provided
10/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of 12 weeks Melatonin administration on depressive symptoms in youth with major depressive disorders - A Randomised, Placebo-controlled, Double-blinded Trial.
Scientific title
The effect of 12 weeks Melatonin administration on depressive symptoms in youth with major depressive disorders - A Randomised, Placebo-controlled, Double-blinded Trial.
Secondary ID [1] 309964 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 330450 0
Sleep Disturbance 330451 0
Condition category
Condition code
Mental Health 327296 327296 0 0
Depression
Mental Health 328700 328700 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment period is 12 weeks for all interventions.
-2mg Melatonin (instant release) or Placebo, 1 tablet to be taken once daily, at night
-Digital Cognitive Behavioural Program, with focus on Insomnia (dCBT-i), to be completed by participant online.
Arm 1 = Melatonin only
Arm 2 =Placebo only
Arm 3 -dCBT-i only
The program includes a weekly 25–45-minute learning session, along with a “homework” assignment and a daily sleep diary (2–4 minutes long). Each weekly session includes a psychoeducational section (e.g., what are the risk factors for insomnia), and the presentation and explanation of a weekly task that incorporates various features to engage the user (video, quizzes, personal vignettes, etc.).. Participants can complete in their own time.
Researchers will be able to monitor adherence post-participation.
Intervention code [1] 326379 0
Treatment: Drugs
Intervention code [2] 327245 0
Treatment: Other
Comparator / control treatment
Placebo (Microcrystalline Cellulose) - No dCBT-i
Control group
Placebo

Outcomes
Primary outcome [1] 336386 0
To determine the effect of a 12-week course of 2mg oral melatonin as an adjunct to treatment as usual, relative to placebo and dCBT-I, in effecting depressive symptoms (through the QIDS-A-CR)
Timepoint [1] 336386 0
The primary endpoint will be any changes in depressive symptoms (QIDS-A-CR) from baseline to weeks 4, 8 and 12
Primary outcome [2] 336872 0
To determine the effect of a 12-week course of 2mg oral melatonin as an adjunct to treatment as usual, relative to placebo and dCBT-I, in effecting the clinical trajectory of major depressive disorder (MDD) (through the SCID-5) in young adults (18 to 30 years of age) with moderate-to-severe MDD.
Timepoint [2] 336872 0
The primary endpoint will be any changes to MDD severity (SCID-5) at week 12.
Secondary outcome [1] 428121 0
To determine whether the melatonin or dCBT-I interventions impacts circadian rhythmicity, as measured by the dim-light melatonin onset (DLMO) and actigraphy
Timepoint [1] 428121 0
DLMO and actigraphy data changes from sleep studies completed at baseline, and during final weeks of intervention (DLMO data from sleep study, to be scheduled between Weeks 8-12 - pending participant and sleep lab availability, Actigraphy watch to be worn from weeks 10-12)
Secondary outcome [2] 429606 0
To examine whether the interventions (melatonin or dCBT-I) affect sleep cycle rhythmicity, as demonstrated in actigraphy and polysomnography data.
Timepoint [2] 429606 0
From baseline measurement to weeks 8-12 (exact schedule of follow-up measurement dependent on sleep lab/participant availability)
Secondary outcome [3] 430472 0
To examine whether the interventions (melatonin or dCBT-I) affect pupil responsiveness, as demonstrated in pupillometry results
Timepoint [3] 430472 0
From baseline measurement to post-intervention (Week 12)
Secondary outcome [4] 430473 0
To examine whether the interventions (melatonin or dCBT-I) affect sleep hormone levels in the blood
Timepoint [4] 430473 0
From baseline measurement to post-intervention (Week 12)

Eligibility
Key inclusion criteria
• Aged between 18 and 30 inclusive at the time of providing informed consent
• Current MDD according to the Structured Clinical Interview for DSM-5 (SCID-5)
• Quick Inventory of Depressive Symptomatology, Adolescent version, self-rated (QIDS-A-SR) score > 11, indicating moderate-to-severe MDD, within 14 days of the first treatment visit
• Pittsburgh Sleep Quality Index score >5 (general sleep disturbance) and/or Epworth Sleepiness Scale score >10 (suggestive of hypersomnia) and/or self-reported delayed sleep phase (habitual bed-time between 02:00-06:00) or irregular sleep cycles
• Ability to provide written informed consent (including both adequate intellectual capacity and fluency in the English language)
Minimum age
18 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of psychosis or bipolar type I or II (assessed with SCID-5)
• Use of any form of melatonin or melatonin agonist within six weeks of the first treatment visit
• Self-reported significant impaired kidney/ liver function (i.e., liver/kidney disease diagnosed)
• Self-reported autoimmune conditions (e.g. rheumatoid arthritis, post-organ transplant)
• Risk of difficulty with blood collection (e.g., poor vein visibility, previous incidence of fainting/significant discomfort during blood collection)
• Self-reported sleep, respiratory (e.g., sleep apnoea), neurological, or medical conditions that could contribute to sleep-wake dysfunction
• Self-reported allergy to melatonin or Microcrystalline Cellulose
• Self-reported pregnancy or breastfeeding
• Recent initiation (past 3 months) of new medication
• Presence of a substance use disorder of at least moderate severity (according to DSM-5) within the preceding 6 months
• Acute suicidal behaviour (score of 6 on Comprehensive Assessment of At-Risk Mental States item 7.3)
• Participation in another trial of a sleep or circadian therapy within one month of the trial commencing
• Regular shift work within 60-days prior to entry into the study.
• Recent transmeridian travel across two or more time zones in the past one month


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)
Drug supplier will receive randomisation schedule with active-placebo from external provider, and supply study drug/placebo
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Rrandomisation table created by computer software by external provider
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
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
579
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 314137 0
Charities/Societies/Foundations
Name [1] 314137 0
Wellcome Trust
Country [1] 314137 0
United Kingdom
Primary sponsor type
University
Name
The University of Sydney
Address
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 317098 0
None
Name [1] 317098 0
Address [1] 317098 0
Country [1] 317098 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313273 0
Sydney Local Health District (RPAH Zone)
Ethics committee address [1] 313273 0
King George V Building, Level 9 Missenden Rd, Camperdown NSW 2050
Ethics committee country [1] 313273 0
Australia
Date submitted for ethics approval [1] 313273 0
27/11/2023
Approval date [1] 313273 0
Ethics approval number [1] 313273 0

Summary
Brief summary
Moreover, melatonin is considered safe, cost-effective, and scalable, thus, a justifiable intervention for circadian mood disorders. To counter the previous clinical trials design flaws, the present study will employ a larger sample size allowing for high statistical power of analyses. Additionally, in the proposed target treatment approach, patients will be stratified based on SCRDs (Sleep and Circadian Rhythm Disturbance) to enhance the potential effectiveness of the intervention.

In a recent proof-of-concept study utilizing agomelatine, a melatonin agonist and serotonin antagonist, for the treatment of major depressive disorder, adults with depression had significantly reduced symptoms after the intervention (Robillard et al., 2018). Moreover, sleep disturbances were significantly reduced, and a strong correlation between relative improvements in depression severity and some components of circadian rhythm disturbances was reported (Robillard et al., 2018).

The overall aim of the study is to examine whether melatonin is a more effective early intervention for youth with depression and SCRDs compared to dCBT-I alone. Additionally, the study aims to investigate whether improvements in SCRDs causally mediate changes in depressive symptoms.

The outcomes of this clinical trial will hold significant implications for early intervention in mood disorders. The findings have the potential to validate and strengthen the hypothesis that individuals with circadian depression may respond more favourably to sleep and circadian-based interventions, such as melatonin. This, in turn, could have transformative implications for personalised interventions in the treatment of mood disorders.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127562 0
Prof Ian Hickie
Address 127562 0
Brain & Mind Centre - The University of Sydney, 100 Mallett St Camperdown NSW 2050
Country 127562 0
Australia
Phone 127562 0
+61 2 9351 0810
Fax 127562 0
Email 127562 0
ian.hickie@sydney.edu.au
Contact person for public queries
Name 127563 0
Mr Nathan Bradshw
Address 127563 0
Brain & Mind Centre - The University of Sydney, 100 Mallett St Camperdown NSW 2050
Country 127563 0
Australia
Phone 127563 0
+61 2 8036 5270
Fax 127563 0
Email 127563 0
nathan.bradshaw@sydney.edu.au
Contact person for scientific queries
Name 127564 0
Mr Nathan Bradshw
Address 127564 0
Brain & Mind Centre - The University of Sydney, 100 Mallett St Camperdown NSW 2050
Country 127564 0
Australia
Phone 127564 0
+61 2 8036 5270
Fax 127564 0
Email 127564 0
nathan.bradshaw@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.