ANZCTR - Registration

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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 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]

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

Condition category

Condition code

Mental Health

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]

Treatment: Drugs

Intervention code [2]

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]

Change in the Montgomery-Asberg Depression Rating Scale (MADRS) at week 12

Timepoint [1]

week 12

Secondary outcome [1]

Change in self-rated depressive symptoms, assessed with the Quick Inventory of Depression Symptomatology (QIDS), at 12 and 26 weeks.

Timepoint [1]

Baseline, week 4, week 8 and week 12

Secondary outcome [2]

Response to treatment, defined as Clinical Global Impression
Improvement score of less than or equal to 2, at 12 weeks.

Timepoint [2]

Week 4, week 8 and week 12

Secondary outcome [3]

Change in score on the Social and Occupational Functioning Scale at 12 and 26 weeks

Timepoint [3]

Baseline and week 12

Secondary outcome [4]

Change in score on the Quality of Life Enjoyment and Satisfaction Questionnaire at 12 weeks

Timepoint [4]

Baseline and week 12

Secondary outcome [5]

Change in score on the Suicidal Ideation Questionnaire at 12 weeks

Timepoint [5]

Baseline, week 4, week 8 and week 12

Secondary outcome [6]

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]

Baseline and then weekly between weeks 1 and 12

Secondary outcome [7]

Change in the Montgomery-Asberg Depression Ratig Scale (MADRS) at 26 weeks.

Timepoint [7]

26 weeks

Secondary outcome [8]

Client reaching remission as defined by MADRAS score of less than or equal to 7 at week 12.

Timepoint [8]

week 12

Secondary outcome [9]

Client reaching remission as defined by MADRAS score of less than or equal to 7 at week 26.

Timepoint [9]

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?

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]

3052

Recruitment postcode(s) [2]

3020

Recruitment postcode(s) [3]

3046

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Funding source category [2]

Government body

Name [2]

National Health and Medical Research Council

Address [2]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [2]

Australia

Primary sponsor type

Other

Name

Orygen Youth Health Research Centre

Address

35 Poplar Road
Parkville, Victoria, 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

University of Melbourne, Melbourne Neuropsychiatry Centre

Address [1]

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]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

MELBOURNE HEALTH HUMAN RESEARCH ETHICS COMMITTEE

Ethics committee address [1]

Office for Research
6 East, Central Building
The Royal Melbourne Hospital
300 Grattan Street
PARKVILLE  VIC  3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

04/10/2012

Approval date [1]

25/10/2012

Ethics approval number [1]

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

Prof Christopher Davey

Address

University of Melbourne

Country

Australia

Phone

+61 383445509

Fax

c.davey@unimelb.edu.au

Contact person for public queries

Name

Christopher Davey

Address

University of Melbourne

Country

Australia

Phone

+61 383445509

Fax

c.davey@unimelb.edu.au

Contact person for scientific queries

Name

Christopher Davey

Address

University of Melbourne

Country

Australia

Phone

+61 383445509

Fax

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.	Type	Citation	Link	Email	Other Details	Attachment
20770	Study protocol		https://trialsjournal.biomedcentral.com/articles/10.1186/1745-6215-15-425

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): Study protocol for a randomised control trial.	2014	https://dx.doi.org/10.1186/1745-6215-15-425
Embase	The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial.	2019	https://dx.doi.org/10.1016/S2215-0366%2819%2930215-9
Embase	Relationships Between Different Dimensions of Social Support and Suicidal Ideation in Young People with Major Depressive Disorder.	2021	https://dx.doi.org/10.1016/j.jad.2020.11.085
Embase	Trajectories 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.	2021	https://dx.doi.org/10.1177/0004867421998763

N.B. These documents automatically identified may not have been verified by the study sponsor.

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