Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613001352796
Ethics application status
Approved
Date submitted
6/12/2013
Date registered
11/12/2013
Date last updated
27/10/2023
Date data sharing statement initially provided
27/10/2023
Date results information initially provided
27/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Youth Depression Alleviation: A randomised controlled trial of omega-3 fatty acids (fish oil) for major depressive disorder in young people (YoDA-F)
Scientific title
Youth Depression Alleviation: A randomised controlled trial of omega-3 fatty acids (fish oil) for major depressive disorder in young people (YoDA-F)
Secondary ID [1] 283505 0
None
Universal Trial Number (UTN)
Trial acronym
YoDA-F
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major depressive disorder 290423 0
Condition category
Condition code
Mental Health 290815 290815 0 0
Depression
Alternative and Complementary Medicine 290816 290816 0 0
Other alternative and complementary medicine

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive either long-chain omega-3 fatty acids or placebo for 12 weeks. All participants will receive cognitive behavioural case management (CBCM). Long-chain omega-3 fatty acids / placebo treatment will commence at week 0. CBCM sessions will commence at approximately week 2.

Cognitive behavioural case management (CBCM): Participants are expected to receive 5 sessions of CBCM. The CBCM intervention consists of cognitive-behavioural therapy (CBT) embedded within case management. The treating clinicians will use a specifically developed manual that details the CBCM to be delivered in the trial, and which outlines the minimum standard of treatment to be delivered. CBCM sessions will be of 50 minutes duration, and will be scheduled on a fortnightly basis (at approximately Weeks 2, 4, 6, 8, 10). The total number of CBCM sessions delivered will be captured for each client. The maximum number of CBCM sessions to be provided is 5. Additional sessions for crisis management will be provided if necessary.

In addition, fidelity will be monitored by therapists rating their own sessions on an established checklist of therapeutic interventions. Any additional interventions delivered will also be documented. The case management component will consist of therapists addressing current interpersonal and social issues.

Active treatment - omega-3 fatty acids: The active treatment is a supplement containing concentrated marine fish oil. The daily dose of 4 capsules will provide approximately 840 mg of eicosapentaenoic acid (EPA), approximately 560 mg of docosahexaenoic acid (DHA), and approximately 5 mg of Vitamin E. Vitamin E is added as an antioxidant to fish oil capsules to stabilize highly unsaturated fatty acids. Participants will receive either 4 capsules of marine fish oil or 4 capsules of approximately 700 mg of paraffin oil (which is not absorbed by the gastrointestinal tract) per day. The daily dose omega-3 fatty acids is based on previous trials in major depression.

Patient compliance will be assessed by monthly pill counts over the course of the study, as well as through self report and the measurement of the fatty acid composition of red blood cell membranes from blood samples collected at baseline and 12 weeks after study entry. The blood samples will be stored frozen for batched analysis. The results of the fatty acid analysis will not be revealed to the investigator until the end of the study.
Intervention code [1] 288211 0
Treatment: Other
Intervention code [2] 288430 0
Behaviour
Comparator / control treatment
Placebo: The placebo are capsules matched in appearance and taste to the active treatment. Placebo capsules contain paraffin oil, chosen as it does not contain polyunsaturated fatty acids and has no impact on omega-3 fatty acid metabolism. To ensure blinding, placebo capsules will be carefully matched in appearance and flavour with the active treatment; they will also contain the same amount of Vitamin E as the fish oil capsules, and approximately 1% fish oil to mimic taste.
Control group
Placebo

Outcomes
Primary outcome [1] 290810 0
Change in depressive symptoms at end of oral intervention phase (12 weeks), as assessed by the 17-item clinician-rated Quick Inventory of Depression Symptoms - Adolescent Version (QIDS-A17-C).
Timepoint [1] 290810 0
Change in QIDS-A17-C scores, between baseline and 12 weeks or the time point when a subject exits the study.
Secondary outcome [1] 305345 0
Change in depressive symptoms at 26-week follow-up, as assessed by the 17-item clinician-rated Quick Inventory of Depression Symptoms - Adolescent Version (QIDS-A17-C).
Timepoint [1] 305345 0
Change in QIDS-A17-C scores, between baseline and 26 weeks.
Secondary outcome [2] 305346 0
Remission rate (defined as patients not meeting diagnostic criteria for major depressive disorder). Additional secondary analyses will compare rates of progression to Stage 2 disorders under active and placebo treatment and length of time to transition.
Timepoint [2] 305346 0
Rates will be assessed at 12-week and 26-week follow-ups.
Secondary outcome [3] 305347 0
Changes to symptomology and psychosocial functioning assessed across a range of domains including: mania (as assessed by the Young Mania Rating Scale; YMRS, and the Altman Self-Report Mania Screen), suicidality and self-harm (as assessed by the Columbia Suicide Severity Rating Scale; C-SSRS), social and occupational functioning (as assessed by the Social and Occupational Functioning Assessment Schedule; SOFAS), psychological distress (as assessed by the Kessler Distress Scale; K10), anxiety (as assessed by the Overall Anxiety Severity and Impairment Scale; OASIS, and Generalized Anxiety Disorder Assessment; GAD-7), and substance use (as assessed by the Alcohol, Smoking And Substance Involvement Screening Test; ASSIST).
Timepoint [3] 305347 0
Assessed at baseline, and weeks 4, 8, 12, and 26.
Secondary outcome [4] 305764 0
Changes to biochemical assessments: oxidative stress (e.g., superoxide dismutase, glutathione, glutathione peroxidase, catalase), cytokines (e.g., interleukin-1, interleukin-6), phospholipase A2 and fasting erythrocyte membrane fatty acid/phospholipid composition, as assessed by mass spectrometry.
Timepoint [4] 305764 0
Changes to biochemical assessments between baseline and 12 weeks.

Eligibility
Key inclusion criteria
1) Aged 15-25 years help seeking for psychological distress.
2) A score between 11 and 20 on the QIDS-A17-C at first contact with the service AND after 1 week (plus 1-5 days if the client is unable to attend earlier) at the second assessment, or at 2 subsequent (weekly) follow-up assessments.
3) A diagnosis of major depressive disorder using the Structured Clinical Interview for DSM-IV Axis I Disorders, patient version (SCID-I/P).
4) Written informed consent (for individuals under 18, written informed consent of at least one parent or a guardian is required).
Minimum age
15 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Lifetime diagnosis or history of treatment for psychotic disorder or bipolar disorder or substance dependence (assessed with a brief, self-developed checklist).
2) History of treatment with an antidepressant (more than four weeks during the last 12 months, upon review of medical history).
3) Acute suicidal behaviour as assessed by a score of 6 on the Comprehensive Assessment of At Risk Mental States (CAARMS; item 7.3) or aggressive behaviour (score of 6 on CAARMS item 5.4).
4) Depression secondary to a medical condition.
5) IQ<70 as per medical history review.
6) Pregnancy or lactation.
7) Laboratory values more than 15% outside the normal range for bleeding parameters.
8) Individuals who are taking omega-3 supplements or psychotropic medication, currently or within 8 weeks of being included in the trial, for more than 1 week continuously.
9) Known allergy to omega-3s or any ingredients in the investigational product.

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)
Eligible participants will be randomised to one of the two treatment groups. Permuted block randomisation numbers will be programmed into a web-based electronic case report form (eCRF) by an independent statistician. Once a research assistant has entered all the requisite inclusion information into the eCRF, they will be able to initiate randomisation. At this point, an automatically generated email will be sent directly to the clinical trial pharmacy. Based on the notification within the body of the email, the pharmacist will allocate the participant to either omega-3 fatty acids or placebo. The randomisation process will be blinded, and only the pharmacist will know which group the participant has been allocated to. It will not be possible for any study staff, or participants to reliably predict with treatment group they have been allocated to.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be computer-generated. The randomisation will be stratified by site, age (less that 18 years, 18 years and above) and sex (male, female).
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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/02/2014
Actual
30/05/2014
Date of last participant enrolment
Anticipated
1/02/2016
Actual
6/12/2019
Date of last data collection
Anticipated
Actual
6/06/2020
Sample size
Target
300
Accrual to date
Final
233
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 1648 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 7531 0
2050 - Camperdown
Recruitment postcode(s) [2] 7532 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 288209 0
Government body
Name [1] 288209 0
National Health and Medical Research Council
Country [1] 288209 0
Australia
Funding source category [2] 288210 0
Other Collaborative groups
Name [2] 288210 0
beyondblue
Country [2] 288210 0
Australia
Primary sponsor type
Other
Name
Orygen Youth Health Research Centre
Address
35 Poplar Road, Parkville VIC 3052
Country
Australia
Secondary sponsor category [1] 286933 0
None
Name [1] 286933 0
Address [1] 286933 0
Country [1] 286933 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290118 0
University of Sydney Human Research Ethics Committee
Ethics committee address [1] 290118 0
University of Sydney
NSW 2006
Ethics committee country [1] 290118 0
Australia
Date submitted for ethics approval [1] 290118 0
02/08/2013
Approval date [1] 290118 0
28/08/2013
Ethics approval number [1] 290118 0
2012/2920

Summary
Brief summary
Long-chain omega-3 polyunsaturated fatty acids (PUFAs) play an important role in a range of physiological processes in all living organisms. Supplementation with omega-3 PUFAs has been shown to have range of beneficial effects on both physical and mental health, while results of previous trials in child and adult populations suggest that omega-3 PUFAs may offer a safe and effective treatment for depression. However, conclusions from these trials have been limited by their relatively small sample sizes. This study aims to test the therapeutic effects of a 12-week randomised, placebo controlled trial of approximately 1.4 grams/day omega-3 fatty acids in 300 help-seeking 15 to 25 year olds presenting with moderate to severe major depressive disorder (MDD).

The primary hypothesis is that young people with moderate-to-severe MDD will show greater improvement after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management (CBCM) compared to treatment with placebo plus CBCM. The primary outcome measure is change in the Quick Inventory of Depression Symptomatology (QIDS-A17-C) score. The secondary hypotheses include the rate of remission (defined as patients not meeting the criteria for MDD at 12 weeks and 6 months) will be greater for young people treated with omega-3 PUFAs plus CBCM compared to treatment with placebo plus CBCM.
Trial website
Nil
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44054 0
A/Prof G Paul Amminger, MD, PhD, FRANZCP
Address 44054 0
Orygen, 35 Poplar Road Parkville, VIC 3052
Country 44054 0
Australia
Phone 44054 0
+61 399669100
Fax 44054 0
Email 44054 0
[email protected]
Contact person for public queries
Name 44055 0
Prof Paul Amminger
Address 44055 0
Orygen, 35 Poplar road, Parkville VIC 3052
Country 44055 0
Australia
Phone 44055 0
+61 399669100
Fax 44055 0
Email 44055 0
[email protected]
Contact person for scientific queries
Name 44056 0
A/Prof G Paul Amminger, MD, PhD, FRANZCP
Address 44056 0
Orygen, 35 Poplar road, Parkville VIC 3052
Country 44056 0
Australia
Phone 44056 0
+61 399669100
Fax 44056 0
Email 44056 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All individual participant data after de-identification
When will data be available (start and end dates)?
Data are available immediately for an indefinite time
Available to whom?
Data will potentially be available to researchers from not-for profit organisations, commercial organisations or other based in any location. All data requests will be considered by the data custodian and the primary sponsor on a case-by-case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted. For further information, see Orygen data sharing policy.
Available for what types of analyses?
To any type of analyses. Assessed on a case-by-case basis.
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health). Search for the ACTRN number in the catalogue to find datasets associated with this trial.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20768Study protocol https://onlinelibrary.wiley.com/doi/abs/10.1111/eip.12166 



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Amminger GP, Rice S, Davey CG, Quinn AL, Hermens D... [More Details]

Documents added automatically
No additional documents have been identified.