Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001281886
Ethics application status
Approved
Date submitted
30/11/2012
Date registered
11/12/2012
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 Cognitive Behavioural Therapy with Fluoxetine or Placebo (YoDA-C)
Scientific title
Youth Depression Alleviation: A Randomised Controlled Trial of Cognitive Behavioural Therapy with Fluoxetine or Placebo (YoDA-C)
Secondary ID [1] 281487 0
Nil
Universal Trial Number (UTN)
U1111-1136-6261
Trial acronym
YoDA-C
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 287752 0
Condition category
Condition code
Mental Health 288093 288093 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cognitive Behavioural Therapy (CBT) will be administered once a week, over a period of 12 weeks

Antidepressant fluoxetine hydrochloride or a placebo tablet will be administered in conjunction with CBT over a period of 12 weeks. The starting dose of fluoxetine or placebo will be 1 capsule or 20mg, administered orally. The dose may be increased at week 5 of the study to a maximum dose of 2 capsules or 40 mg.

Each treatment session will last 45 to 50 minutes. Typically, an individual CBT session comprises 3 components. The first third of the session is devoted to reviewing the take-home practice activities and setting an agenda for the current session by reviewing mood, events, incidents or issues that have arisen during the previous week. The middle third of the session is devoted to the skill to be taught that week, linking it with any issues or incidents raised in the first third of the session. The final third of the session addresses issues that have been generated in the first third of the session, and plans are made for the next take-home practice activity.
It is anticipated that all therapists will attend fortnightly supervision sessions with senior clinicians. The fidelity of CBT treatment will be assessed throughout the trial to ensure that the treatment delivered by the trial therapists adheres to the CBT manual. Each CBT session will be recorded, and the de-identified recording will be stored on the OYHRC secure server. A random session from the course of therapy for each participant will be independently rated by an expert CBT practitioner using specifically designed scales for measuring CBT fidelity

Participants will commence on 1 tablet of fluoxetine 20 mg or 1 tablet of the placebo pill. The medication can be increased to fluoxetine 40 mg daily (or 2 placebo pills) if there has been a poor clinical response after the first 4 weeks. The medication will be prescribed by the treating doctor after the baseline visit has been completed and the participant has been randomised. The trial medications will be supplied on a 4-weekly basis by the RMH Royal Park Campus pharmacy, with a total of 3 dispensations per patient
Intervention code [1] 285996 0
Treatment: Drugs
Intervention code [2] 285997 0
Behaviour
Comparator / control treatment
Placebo will be administered as a control treatment instead of fluoxetine. Placebo capsules will be made of Microcrystalline Cellulose and matched in appearance to the fluoxetine medication (all manufacturing will be conducted under Good Manufacturing Practice-GMP). It will be administered orally and in conjunction with CBT over a period of 12 weeks. The starting dose will be 1 capsule or 20mg of placebo, which may be increased at week 5 of the study to a maximum dose of 2 capsules or 40 mg of placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 288301 0
Change in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 12
Timepoint [1] 288301 0
week 12
Secondary outcome [1] 299785 0
Change in self-rated depressive symptoms, assessed with the Quick Inventory of Depression Symptomatology (QIDS), at 12 and 26 weeks.
Timepoint [1] 299785 0
Baseline, week 4, week 8 and week 12
Secondary outcome [2] 299786 0
Response to treatment, defined as Clinical Global Impression
Improvement score of less than or equal to 2, at 12 weeks.
Timepoint [2] 299786 0
Week 4, week 8 and week 12
Secondary outcome [3] 299787 0
Change in score on the Social and Occupational Functioning Scale at 12 and 26 weeks
Timepoint [3] 299787 0
Baseline and week 12
Secondary outcome [4] 299788 0
Change in score on the Quality of Life Enjoyment and Satisfaction Questionnaire at 12 weeks
Timepoint [4] 299788 0
Baseline and week 12
Secondary outcome [5] 299789 0
Change in score on the Suicidal Ideation Questionnaire at 12 weeks
Timepoint [5] 299789 0
Baseline, week 4, week 8 and week 12
Secondary outcome [6] 299790 0
Proportion of patients showing an increase in suicidal ideation, or displaying suicidal behaviour, on the Columbia Suicide Severity Rating Scale (C-SSRS) at any assessment during the 12-week treatment period
Timepoint [6] 299790 0
Baseline and then weekly between weeks 1 and 12
Secondary outcome [7] 300825 0
Change in the Montgomery-Asberg Depression Ratig Scale (MADRS) at 26 weeks.
Timepoint [7] 300825 0
26 weeks
Secondary outcome [8] 300826 0
Client reaching remission as defined by MADRAS score of less than or equal to 7 at week 12.
Timepoint [8] 300826 0
week 12
Secondary outcome [9] 300827 0
Client reaching remission as defined by MADRAS score of less than or equal to 7 at week 26.
Timepoint [9] 300827 0
week 26

Eligibility
Key inclusion criteria
Aged between 15 and 25 years inclusive:
Diagnosis of Major Depressive Disorder (MDD) using Structured Clinical Interview for DSM-IV Axis I Disorders, patient version (SCID);
Score on the MADRS of 20 or greater, indicating depression of at least moderate severity;
Ability to provide written informed consent
Minimum age
15 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
First episode psychosis (at least one positive symptom occurring daily for at least one week, or at least three times per week if the symptom lasts for longer than one hour on each occasion);
Lifetime or current SCID-I diagnosis of bipolar I or II disorder;
Acute or unstable medical disorder that would interfere with treatment;
Severe disturbance such that the young person would be unable to comply with the requirements of informed consent or comply with the study protocol;
Current treatment with an antidepressant medication for at least 2 weeks;
Previous treatment with fluoxetine that was either ineffective or poorly tolerated

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)
After the baseline assessment has been completed, the participant will be randomised to one of the two treatment groups. A randomisation list has been generated by an independent, unblinded statistician and passed onto the electronic database technician/designer. Therefore, allocation concealment is performed via central randomisation by a computer, which will then be inputted into the eCRF by the technician. Upon randomisation, an email will be sent directly to the pharmacy specifying whether the participant should be allocated fluoxetine or placebo. Participants will be randomised sequentially (within the applicable stratum based on site, age and gender information) as they become eligible for randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation will be enabled by computer generated numbers programmed into the electronic CRF (eCRF) by an independent statistician.The randomisation will be stratified by site, age and gender.
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 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/01/2013
Actual
18/02/2013
Date of last participant enrolment
Anticipated
Actual
9/12/2016
Date of last data collection
Anticipated
Actual
21/07/2017
Sample size
Target
260
Accrual to date
Final
153
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 5936 0
3020
Recruitment postcode(s) [2] 5937 0
3046
Recruitment postcode(s) [3] 5935 0
3052

Funding & Sponsors
Funding source category [1] 286262 0
Government body
Name [1] 286262 0
National Health and Medical Research Council
Country [1] 286262 0
Australia
Funding source category [2] 286263 0
Government body
Name [2] 286263 0
National Health and Medical Research Council
Country [2] 286263 0
Australia
Primary sponsor type
Other
Name
Orygen Youth Health Research Centre
Address
35 Poplar Road
Parkville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 285062 0
None
Name [1] 285062 0
Address [1] 285062 0
Country [1] 285062 0
Other collaborator category [1] 277152 0
University
Name [1] 277152 0
University of Melbourne, Melbourne Neuropsychiatry Centre
Address [1] 277152 0
Alan Gilbert Building, The University of Melbourne, 161 Barry Street, Carlton South, Victoria, 3053.

and
Sunshine Hospital, PO Box 294, St Albans, VIC, 3021
Country [1] 277152 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288338 0
MELBOURNE HEALTH HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 288338 0
Office for Research
6 East, Central Building
The Royal Melbourne Hospital
300 Grattan Street
PARKVILLE VIC 3050
Ethics committee country [1] 288338 0
Australia
Date submitted for ethics approval [1] 288338 0
04/10/2012
Approval date [1] 288338 0
25/10/2012
Ethics approval number [1] 288338 0
2012.134

Summary
Brief summary
The aim of this NHMRC-funded study is to answer an important question in the treatment of moderate-to-severe youth depression: should antidepressant treatment be started as a first-line treatment, concurrent with psychotherapy? The question has taken on increased clinical importance in the wake of recent evidence questioning the efficacy and safety of antidepressants in young people, and the subsequent development of treatment guidelines for youth depression that provide only qualified support for their use.

This proposal aims to address the need for studies of effective treatments for youth with moderate to severe major depressive disorder (MDD). Patients between the ages of 15 and 25 will be randomised to receive either (i) cognitive behavioural therapy (CBT) and fluoxetine, or (ii) CBT and placebo, for 12 weeks in a double-blind, randomised controlled trial (RCT), with followup to 26 weeks.

This will be the first placebo-controlled study that has examined whether the addition of medication to CBT is a more effective strategy than the provision of CBT alone for the treatment of youth depression.

The primary hypothesis is that young people with moderate to severe MDD will show greater improvement after 12
weeks of treatment with CBT and fluoxetine (CBT+FLX) compared to treatment with CBT and placebo (CBT+PBO).
The primary outcome measure is change in the MontgomeryAsberg Depression Rating Scale (MADRS), an
observerrated depression scale that is widely used in depression treatment trials, being both easy to administer
and psychometrically sound (Montgomery & Asberg, 1979).
Our secondary hypotheses are that the CBT+FLX group will show greater improvement compared to the CBT+PBO
group on efficacy, functioning, quality of life, and safety measures at 12 weeks, but that the differences between
groups will not be sustained at 26 weeks.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34910 0
Prof Christopher Davey
Address 34910 0
University of Melbourne
Country 34910 0
Australia
Phone 34910 0
+61 383445509
Fax 34910 0
Email 34910 0
c.davey@unimelb.edu.au
Contact person for public queries
Name 18157 0
Prof Christopher Davey
Address 18157 0
University of Melbourne
Country 18157 0
Australia
Phone 18157 0
+61 383445509
Fax 18157 0
Email 18157 0
c.davey@unimelb.edu.au
Contact person for scientific queries
Name 9085 0
Prof Christopher Davey
Address 9085 0
University of Melbourne
Country 9085 0
Australia
Phone 9085 0
+61 383445509
Fax 9085 0
Email 9085 0
c.davey@unimelb.edu.au

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 following 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
20770Study protocol https://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-15-425 


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Davey CG, Chanen AM, Hetrick SE, Cotton SM, Rathee... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial.2019https://dx.doi.org/10.1016/S2215-0366%2819%2930215-9
EmbaseRelationships Between Different Dimensions of Social Support and Suicidal Ideation in Young People with Major Depressive Disorder.2021https://dx.doi.org/10.1016/j.jad.2020.11.085
EmbaseTrajectories of change in depression symptoms and suicidal ideation over the course of evidence-based treatment for depression: Secondary analysis of a randomised controlled trial of cognitive behavioural therapy plus fluoxetine in young people.2021https://dx.doi.org/10.1177/0004867421998763
EmbaseThe addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): Study protocol for a randomised control trial.2014https://dx.doi.org/10.1186/1745-6215-15-425
N.B. These documents automatically identified may not have been verified by the study sponsor.