ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619001412123

Ethics application status

Approved

Date submitted

20/09/2019

Date registered

15/10/2019

Date last updated

4/08/2023

Date data sharing statement initially provided

15/10/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Preventing relapse of major depressive disorder in youth: Randomised Controlled Trial of a novel mindfulness-based cognitive online social therapy

Scientific title

Preventing relapse of major depressive disorder in youth: RCT of a novel mindfulness-based cognitive online social therapy

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1225-9470

Trial acronym

Linked study record

This record is the pilot study of the current study.
Rice, S. et al. 2016. Moderated online social therapy for depression relapse prevention in young people: pilot study of a 'next generation' online intervention. Early Interv Psychiatry.

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

The intervention under investigation is a moderated online social networking system, called Rebound. Rebound is an online intervention specifically designed to prevent relapse in youth Major Depressive Disorder (MDD) and includes therapeutic activities and information about mental health, mindfulness, personal strengths, and other topics relevant for young people recovering from MDD. Rebound also includes a social network where participants can communicate via posts and comments in a news feed and a problem-solving forum.

The online platform will be moderated by experienced mental health workers based at Orygen Youth Health. Trained peer workers with lived experience of mental ill-health will also provide support to participants through the Rebound social network.

Following randomisation, participants allocated to the Rebound intervention will complete an online orientation and follow-up phone call with the online moderator. Participants will access Rebound (including individualised therapist support) for 18 months. During this period, participants may access Rebound as often as they like, at any time, from any internet-enabled device.

Rebound integrates online personal therapist support (by clinical psychologists). Their role is to provide guidance, monitor participant’s activity and clinical status and ensure the safety of the social network. Each therapist is assigned a caseload, which they follow for the duration of the trial. Moderators send each client tailored content suggestions weekly (e.g. a module or action) based on their needs and interests. Clients can rate the helpfulness of the suggestions, which moderators use to recommend subsequent content. Participant logins are monitored by the moderator. When a participant has not logged in for more than 7 days, this will be reviewed at moderator supervision.

To promote engagement, retention of participants, and behavioural change, Rebound was developed following persuasive system design including primary task support (i.e., modularisation and personalisation of content), social support (i.e., fully integrated, purpose-built social network) and dialogue support (i.e., reward provided by therapists, peer-supporters and automated functions).

Users will be invited by moderators to meet other users at ‘Rebound meet-ups’. Meet-ups will consist of an interactive 1-hour session on ‘how to make Rebound work for you’ and will provide users with the opportunity to ask questions and give feedback on the system. Participants will be reimbursed for their time.

In the event of a clinically significant deterioration of depressive symptoms, increased risk or a hospital admission, the clinical moderators in conjunction with the CI team will perform an assessment to determine the risks and benefits of a temporary withdrawal from Rebound. Based on this assessment, and in consultation with the young person, the team will determine whether the account is temporarily suspended, or level of access restricted (e.g., participant can access therapeutic content and support from moderators, and view content in the social network, but cannot post comments or participate in existing threads within the social network). All instances of depressive relapse will be reported to the Project Manager and recorded as an Adverse Event. Following suspensions or restrictions to a user’s account, the study coordinator or moderator will contact the young person at fortnightly intervals to ascertain whether the account is to be reactivated.

All participant activity (frequency, duration, pattern of use etc.) on the system is recorded by system data analytics.

Intervention code [1]

Prevention

Intervention code [2]

Treatment: Other

Intervention code [3]

Behaviour

Comparator / control treatment

Treatment As Usual (TAU) consists of a range of treatment options delivered by Youth Mood Clinic, Orygen Youth Health or headspace treating teams prior to discharge or, after discharge, generic medical or mental health services typically available to young people in the absence of enrolment in the study. These can include follow-up by a general practitioner, private psychiatrist, primary care youth mental health services, or adult mental health services which deliver multidisciplinary psychiatric care (including medical follow-up, case management and acute psychiatric care as appropriate). To ensure the consistency and quality of TAU, online psychoeducation will be offered to those allocated to the control group (enhanced TAU). Psychoeducation is beneficial as an adjunct treatment for depression and is readily translated into web-format (Tursi et al., 2013). We have developed Empower Your Mood (EYM), a web application that includes psycho-education modules on depression symptoms, causes and course, behaviour and mood, information on diet, exercise, sleep, social support and getting support. EYM does not include therapist support or online social networking. All modules will be available for 18 months to match Rebound’s time frame.

Control group

Active

Outcomes

Primary outcome [1]

The primary outcome is relapse rate of Major Depressive Disorder (MDD). Relapse will be defined as a return, for at least 2 weeks, of symptoms sufficient to meet DSM-5 criteria for MDD (as determined by the SCID-5-RV) at any time in the 18 months post-baseline.

Timepoint [1]

Baseline, then 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (primary timepoint) after randomisation. Baseline, 6, 12 and 18 month assessments will be carried out via face-to-face interviews. Assessments at 3, 9 and 15 months, will be conducted over the phone. The accumulated relapse rate across these assessment will constitute the primary outcome.

Secondary outcome [1]

Depressive symptoms will be measured by the Quick Inventory of Depressive Symptomatology (QIDS) self-report instrument.

Timepoint [1]

Baseline and every month post randomisation for 18 months.

Secondary outcome [2]

Time to relapse will be derived from the Depression Module of the SCID-5-RV

Timepoint [2]

Baseline and 3, 6, 9, 12, 15 and 18 months post randomisation.

Secondary outcome [3]

Loneliness will be measured via the UCLA Loneliness Scale (Version 3).

Timepoint [3]

Baseline and 6, 12 and 18 months post randomisation.

Secondary outcome [4]

Anxiety will be measured by the Generalised Anxiety Disorder 7-item scale.

Timepoint [4]

Baseline and 6, 12 and 18 months post randomisation.

Secondary outcome [5]

Social anxiety will be measured via the Liebowitz Social Anxiety Scale.

Timepoint [5]

Baseline and 6, 12 and 18 months post randomisation.

Secondary outcome [6]

Self efficacy will be measured by means of the Self-Efficacy Scale

Timepoint [6]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [7]

Self-esteem will be measured via the 10 item Rosenberg Self-Esteem Scale

Timepoint [7]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [8]

Suicidal ideation and attempts will be measured via the Columbia-Suicide Severity Rating Scale

Timepoint [8]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [9]

Deliberate self-harm will be assessed through the Risk Taking and Self Harm Inventory for Adolescents

Timepoint [9]

Baseline and at 6, 12 and 18 months post randomisation

Secondary outcome [10]

Psychological wellbeing will be assessed by the Basic Psychological Need Satisfaction Questionnaire

Timepoint [10]

Baseline, and at 6, 12 and 18 months post randomisation.

Secondary outcome [11]

Psychosocial functioning will be measured by the Social and Occupational Functioning Assessment Scale (SOFAS).

Timepoint [11]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [12]

Quality of life will be assessed by the Assessment of Quality of Life – Eight Dimension (AQoL-8D)

Timepoint [12]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [13]

To conduct the economic analysis, the AQoL-8D will be used to calculate quality-adjusted life years. AI Mihalopoulos has shown that this is the most sensitive instrument for this purpose to use in depression. The actual cost of the Rebound intervention will be determined and captured using provider records including interviews with key budgetary personnel. A Resource Use Questionnaire (RUQ) will be used to determine the broader resource use of participants including treatment usage. Additionally, information from Medicare and the Pharmaceutical Benefits Schedule (PBS) will be accessed to collect routine data on the use of primary health care services. Data provided by the Centre for Victorian Data Linkage over 18 months follow-up on participant hospital admissions will also contribute to the economic analysis.

Timepoint [13]

The RUQ and AQoL-8D administered at Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [14]

Mindfulness skills will be measured using the Freiburg Mindfulness Inventory.

Timepoint [14]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [15]

Self-compassion will be measured via the Self-Compassion Scale Short Form

Timepoint [15]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [16]

Rumination will be assessed via the Ruminative Responses Scale

Timepoint [16]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [17]

Social support will be measured using the Social Provisions Scale

Timepoint [17]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [18]

Digital phenotype, represented by data collected via a passive sensing application (AWARE) downloaded on the participant’s smartphone. The following sensors will be used in this study:
a. Applications: Captures the applications being used on the smartphone;
b. Communication: Captures the number of incoming/outgoing calls and SMS messages, without recording the content of these calls or messages;
c. Locations: Captures user geolocation;
d. Screen usage: Captures when users lock/unlock their phones and use the screen, including time and duration of phone use. This sensor does not capture what is on the screen at any time;
e. Screen interaction: Captures when a user uses the keyboard, without recording what is typed. This sensor also captures when a user clicks and scrolls on their smartphone;

Timepoint [18]

Continuous from baseline until 9 months post randomisation.

Secondary outcome [19]

Behavioural activation will be measured using the Behavioural Activation for Depression Scale

Timepoint [19]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [20]

Generalised anxiety disorder and worries will be assessed using the Generalised Anxiety Disorder 7-item scale

Timepoint [20]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [21]

Sleep will be measured using the Pittsburg Sleep Quality Index

Timepoint [21]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [22]

Strengths use will be assessed via the Strengths Use Scale

Timepoint [22]

Baseline and at 6, 12 and 18 months post randomisation.

Secondary outcome [23]

Social support, cognitive and affective reactivity (composite secondary outcome) will be measured in real time using Smartphone Ecological Momentary Assessment (SEMA). Ecological Momentary Assessment is the gold-standard for capturing experiences in daily life (Granholm et al., 2013). SEMA will be used to track patients’ mood, rumination, social support and cognitive and affective reactivity once daily for the duration of the intervention period (12 months). SEMA items have been drawn from previous research and adapted (Kircanski et al., 2017, Moberly and Watkins, 2008). SEMA will be administered via a smartphone application designed by CIs Alvarez, Gleeson and Koval. SEMA is available for iOS and Android-based smart phones, enables server-centred configuration (i.e. questionnaires, delivery times and data storage are configurable online) and stores data in real time in secure cloud storage, therefore minimizing loss of data.

Timepoint [23]

Continuous from baseline until 18 months post randomisation.

Secondary outcome [24]

Qualitative evaluation of intervention acceptability will be undertaken via semi-structured interview at end of intervention

Timepoint [24]

Post 18 month assessment.

Secondary outcome [25]

Usage of Rebound (composite secondary outcome) will be measured by data system analytics which will capture usage of the online system over 18 months follow-up (i.e. frequency, duration and patterns of use).

Timepoint [25]

Continuous from Induction until 18 months post randomisation.

Secondary outcome [26]

Therapeutic Alliance will be measured using the Working Alliance Inventory client version (WAI-C). The WAI is a measure of the therapeutic alliance that assesses three key aspects of the therapeutic alliance: (a) agreement on the tasks of therapy, (b) agreement on the goals of therapy and (c) development of an affective bond.

Timepoint [26]

1, 6, 12, 18 months post randomisation,

Secondary outcome [27]

Stress will be measured by the Perceived Stress Scale.

Timepoint [27]

Baseline and 6, 12 and 18 months post randomisation.

Secondary outcome [28]

Time to remission will be derived from the Depression Module of the SCID-5-RV

Timepoint [28]

Baseline and 3, 6, 9, 12, 15 and 18 months post randomisation.

Eligibility

Key inclusion criteria

1. Age 14 to 27 years inclusive;
2. Ability to read and converse in English;
3. Ability to provide informed consent;
4. Ability and willingness to nominate an emergency contact person, such as a close family member;
5. Diagnosis of MDD (current, partial or full remission) Current or previous primary diagnosis of MDD (corresponding with the most recent episode of care);
6. = 1 episode of MDD if in partial remission at time of screening assessment or = 2 episodes of MDD (including the current episode) if current MDD or MDD in full remission at time of screening assessment.

Minimum age

14 Years

Maximum age

27 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Inability to converse in, or read English;
2. Acute risk of self-harm requiring urgent intervention (i.e., suicidal ideation with a current plan and intent to enact this plan);
3. A diagnosed permanent developmental delay or intellectual disability;
4. Current or past episode of mania or hypomania;
5. Previous exposure to a MOST platform.

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)

The randomisation schedule will be generated by a statistician independent of the study.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomisation will be carried out remotely according to the International Conference on Harmonization E9 Statistical Principles Guidelines (Lewis, 1999). Participants will be randomly assigned to the treatment condition using randomly permutated blocks. Patients will be stratified by remission status (full vs. partial remission, as partial remission is an indicator of increased risk of relapse (Kennard et al., 2014)), number of previous MDD episodes (1 or greater than 1), and by treatment centre (YMC, headspace Glenroy, headspace Craigieburn, headspace Sunshine, headspace Werribee, headspace Goulburn, headspace Wollongong, headspace Bega, headspace Nowra, headspace Bondi Junction, Bondi Junction Community Mental Health Centre, Orygen Clinical Trials Unit).

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Sample size was determined by power analysis using G*Power 3. The primary outcome is difference in accumulated relapse rate over 18 months. A previous relapse prevention study in youth MDD reported a relapse rate at 18-months follow-up of 62% for TAU and 36% in the Relapse Prevention group (OR=2.9) (Emslie et al., 2015). Since Rebound is being compared against an enhanced TAU, we assume a smaller effect (OR=2.5), for which a total sample of 192 people is required to achieve 85% power (alpha=0.05). For the secondary outcome measures there will be 93% power to detect medium effect sizes (Cohen's d=0.5). A total of 255 patients will be recruited, allowing for a 25% attrition rate. This compares favourably with the attrition rates in the Rebound pilot (7%) and is comparable at 18-month follow-up to the Horyzons RCT (25%), an RCT of moderated online social therapy in young people with psychosis.

Primary analyses will be undertaken on an intention-to-treat basis. Group differences in accumulated relapse rate at 18-months (primary outcome) will be tested using Fisher’s Exact Test. the Cox proportional hazards regression model (survival analysis) will be used to model time to relapse in each group, which will also be used to derive the hazard function reflecting the instantaneous probability of relapse at any time over the 18-month follow-up. Group differences in change over time in the continuous secondary outcomes across the 18-month follow-up will be examined using random-effects models.

Mechanism of action analyses will be conducted using a multilevel structural equation modelling (MSEM) framework to assess mediation. Specifically, person-specific slopes representing change over time in the proposed mechanism-of-action variables (mindfulness skills, self-compassion, social support and rumination) will be examined as mediators of the effect of treatment group (Rebound vs. control) on risk of relapse. MSEM will be also used to analyse passive sensing data, including the relationship between mobile data and study measures.

Economic evaluation will comprise a cost-consequences analysis whereby incremental costs of the intervention will be compared to the full spectrum of study outcomes. Intervention development costs will be distributed across the estimated potential users of Rebound rather than only trial participants, which would significantly overestimate individual costs. The evaluation will measure and value any change to the use of health care resources over the period of the study between the two treatment arms; and then compare any additional costs to the additional outcomes achieved. We expect Rebound to have sufficient benefits to make it cost-effective at commonly accepted value for money thresholds (e.g., $50,000/ QALY; (Carter et al., 2008). The potentially higher direct cost of Rebound is expected to be offset by a reduction in overall costs (e.g., fewer hospital admissions, less need for community care etc.) Standardised economic evaluation techniques including incremental analysis of mean differences and bootstrapping to determine confidence intervals will be used. If, as expected, the intervention is found to be effective, lifetime and population cost-effectiveness of Rebound will be determined using modelling techniques refined and previously used by AI Mihalopoulos (Mihalopoulos et al., 2011).

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

21/10/2019

Actual

29/10/2019

Date of last participant enrolment

Anticipated

30/09/2023

Actual

Date of last data collection

Anticipated

31/03/2025

Actual

Sample size

Target

255

Accrual to date

231

Final

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment postcode(s) [1]

3052 - Parkville

Recruitment postcode(s) [2]

3064 - Craigieburn

Recruitment postcode(s) [3]

3046 - Glenroy

Recruitment postcode(s) [4]

3020 - Sunshine

Recruitment postcode(s) [5]

3030 - Werribee

Recruitment postcode(s) [6]

2550 - Bega

Recruitment postcode(s) [7]

2500 - Wollongong

Recruitment postcode(s) [8]

2580 - Goulburn

Recruitment postcode(s) [9]

2541 - Nowra

Recruitment postcode(s) [10]

2022 - Bondi Junction

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

16 Marcus Clarke St, Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other

Name

Orygen

Address

35 Poplar Rd, Parkville, VIC, 3052

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health Human Research Ethics Committee

Ethics committee address [1]

Office for Research
Level 2
South West
300 Grattan Street
Parkville 3052 Victoria

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/10/2018

Approval date [1]

21/02/2019

Ethics approval number [1]

HREC/42967/MH-2018

Summary

Brief summary

The study aims to evaluate, via a randomised controlled trial (RCT), the effectiveness of Rebound, a moderated online social networking system in preventing relapse of Major Depressive Disorder (MDD) in young people (aged 14-27) with remitted MDD.

Rebound includes therapeutic activities and information about mental health, mindfulness, personal strengths, and other topics relevant for young people recovering from MDD. Rebound also includes a social network where participants can communicate via posts and comments in a newsfeed and a problem-solving forum. The social network will be moderated by experienced mental health workers and trained peer workers with lived experience of mental ill-health.

Enhanced TAU includes access to a private website with information about depression symptoms, causes and course, the relationship between behaviour and mood, information on diet, exercise, sleep, social support and getting support. Enhanced TAU does not include therapist support or online social networking.

The primary hypothesis of the study is that, relative to enhanced TAU, TAU plus Rebound will reduce relapse rates among remitted young people with MDD.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Mario Alvarez-Jimenez

Address

Orygen, 35 Poplar Rd Parkville VIC 3052

Country

Australia

Phone

+61 0401 772 668

Fax

[email protected]

Contact person for public queries

Name

Mrs Daniela Cagliarini

Address

Orygen, 35 Poplar Rd Parkville VIC 3052

Country

Australia

Phone

+61 0408 607 919

Fax

[email protected]

Contact person for scientific queries

Name

Mrs Daniela Cagliarini

Address

Orygen, 35 Poplar Rd Parkville VIC 3052

Country

Australia

Phone

+61 0408 607 919

Fax

[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 of the individual trial-related participant data collected during the trial, after de-identification.

When will data be available (start and end dates)?

Immediately following publication up and for a further 3 years

Available to whom?

Data are potentially available to:
- Researchers from not-for-profit organisations
- Commercial organisations
- Other
Based in:
- Any location
Further information: All data requests will be considered by 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.

Available for what types of analyses?

Any approved protocol, IPD meta-analysis or systematic review.
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://www.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	Email
4648	Study protocol	[email protected]
4650	Statistical analysis plan	[email protected]
4651	Informed consent form	[email protected]

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.

Trial Review

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