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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
3/09/2024
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] 296932 0
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 310882 0
Condition category
Condition code
Mental Health 309558 309558 0 0
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] 313207 0
Prevention
Intervention code [2] 313208 0
Treatment: Other
Intervention code [3] 313209 0
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] 318513 0
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] 318513 0
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] 365188 0
Depressive symptoms will be measured by the Quick Inventory of Depressive Symptomatology (QIDS) self-report instrument.
Timepoint [1] 365188 0
Baseline and every month post randomisation for 18 months.
Secondary outcome [2] 365189 0
Time to relapse will be derived from the Depression Module of the SCID-5-RV
Timepoint [2] 365189 0
Baseline and 3, 6, 9, 12, 15 and 18 months post randomisation.
Secondary outcome [3] 365190 0
Loneliness will be measured via the UCLA Loneliness Scale (Version 3) as an exploratory outcome.
Timepoint [3] 365190 0
Baseline and 6, 12 and 18 months post randomisation.
Secondary outcome [4] 365191 0
Anxiety will be measured by the Generalised Anxiety Disorder 7-item scale.
Timepoint [4] 365191 0
Baseline and 6, 12 and 18 months post randomisation.
Secondary outcome [5] 365192 0
Social anxiety will be measured via the Liebowitz Social Anxiety Scale as an exploratory outcome.
Timepoint [5] 365192 0
Baseline and 6, 12 and 18 months post randomisation.
Secondary outcome [6] 365193 0
Self-efficacy will be measured via the Self-Efficacy Scale as an exploratory outcome.
Timepoint [6] 365193 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [7] 365194 0
Self-esteem will be measured via the Rosenberg Self-Esteem Scale as an exploratory outcome.
Timepoint [7] 365194 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [8] 365196 0
Suicidal ideation and attempts will be measured via the Columbia-Suicide Severity Rating Scale as an exploratory outcome.
Timepoint [8] 365196 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [9] 365197 0
Deliberate self-harm will be assessed through the Risk Taking and Self Harm Inventory for Adolescents as an exploratory outcome.
Timepoint [9] 365197 0
Baseline and at 6, 12 and 18 months post randomisation
Secondary outcome [10] 365198 0
Psychological wellbeing will be assessed by the Basic Psychological Need Satisfaction Questionnaire as an exploratory outcome.
Timepoint [10] 365198 0
Baseline, and at 6, 12 and 18 months post randomisation.
Secondary outcome [11] 365199 0
Psychosocial functioning will be measured by the Social and Occupational Functioning Assessment Scale (SOFAS). as an exploratory outcome.
Timepoint [11] 365199 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [12] 365200 0
Quality of life will be assessed by the Assessment of Quality of Life – Eight Dimension (AQoL-8D)
Timepoint [12] 365200 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [13] 365201 0
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] 365201 0
The RUQ and AQoL-8D administered at Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [14] 365203 0
Mindfulness skills will be measured using the Freiburg Mindfulness Inventory as a measure of therapeutic mechanism of the intervention.
Timepoint [14] 365203 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [15] 365204 0
Self-compassion will be measured via the Self-Compassion Scale Short Form as a as a measure of therapeutic mechanism of the intervention.
Timepoint [15] 365204 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [16] 365205 0
Rumination will be assessed via the Ruminative Responses Scale as a as a measure of therapeutic mechanism of the intervention.
Timepoint [16] 365205 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [17] 365206 0
Social support will be measured using the Social Provisions Scale as a measure of therapeutic mechanism of the intervention.
Timepoint [17] 365206 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [18] 365207 0
Digital phenotype is an exploratory outcome, 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] 365207 0
Continuous from baseline until 9 months post randomisation.
Secondary outcome [19] 365208 0
Behavioural activation will be measured using the Behavioural Activation for Depression Scale as an exploratory outcome.
Timepoint [19] 365208 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [20] 365209 0
Generalised anxiety disorder and worries will be assessed using the Generalised Anxiety Disorder 7-item scale as an exploratory outcome.
Timepoint [20] 365209 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [21] 365210 0
Sleep will be measured using the Pittsburg Sleep Quality Index as an exploratory outcome.
Timepoint [21] 365210 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [22] 365211 0
Strengths use will be assessed via the Strengths Use Scale as an exploratory outcome
Timepoint [22] 365211 0
Baseline and at 6, 12 and 18 months post randomisation.
Secondary outcome [23] 365212 0
Social support, cognitive and affective reactivity will be measured in real time using Smartphone Ecological Momentary Assessment (SEMA) as an exploratory outcome. 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] 365212 0
Continuous from baseline until 12 months post randomisation.
Secondary outcome [24] 365215 0
Qualitative evaluation of intervention acceptability will be undertaken via semi-structured interview at end of intervention
Timepoint [24] 365215 0
Post 18 month assessment.
Secondary outcome [25] 365216 0
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] 365216 0
Continuous from Induction until 18 months post randomisation.
Secondary outcome [26] 374561 0
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] 374561 0
1, 6, 12, 18 months post randomisation,
Secondary outcome [27] 375378 0
Stress will be measured by the Perceived Stress Scale.
Timepoint [27] 375378 0
Baseline and 6, 12 and 18 months post randomisation.
Secondary outcome [28] 416896 0
Time to remission will be derived from the Depression Module of the SCID-5-RV
Timepoint [28] 416896 0
Baseline and 3, 6, 9, 12, 15 and 18 months post randomisation.
Secondary outcome [29] 439369 0
Rate of remission will be derived from the Depression Module of the SCID-5-RV. This addition was added to more fully understand the complexity of relapse in Major Depressive Disorder in young people.
Timepoint [29] 439369 0
Secondary outcome [30] 439370 0
Rate of remission will be derived from the Depression Module of the SCID-5-RV. This addition was added to more fully understand the complexity of relapse in Major Depressive Disorder in young people.
Timepoint [30] 439370 0
Baseline and 3, 6, 9, 12, 15 and 18 months post randomisation.
Secondary outcome [31] 439371 0
Vocational status as self-reported by participants
Timepoint [31] 439371 0
Baseline and 3, 6, 9, 12, 15 and 18 months post randomisation.
Secondary outcome [32] 439372 0
Vocational status as self-reported by participants
Timepoint [32] 439372 0
Baseline, 6, 12 and 18 months post randomisation.
Secondary outcome [33] 439373 0
Time in remission will be derived from the SCID-5-RV (Module A – Mood Episodes)
Timepoint [33] 439373 0
Baseline, 6, 12 and 18 months post randomisation.
Secondary outcome [34] 439374 0
Time in remission will be derived from the SCID-5-RV (Module A – Mood Episodes)
Timepoint [34] 439374 0
Baseline, 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?
No
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
Active, not recruiting
Date of first participant enrolment
Anticipated
21/10/2019
Actual
29/10/2019
Date of last participant enrolment
Anticipated
30/09/2023
Actual
29/09/2023
Date of last data collection
Anticipated
31/03/2025
Actual
Sample size
Target
255
Accrual to date
Final
246
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment postcode(s) [1] 25349 0
3052 - Parkville
Recruitment postcode(s) [2] 25350 0
3064 - Craigieburn
Recruitment postcode(s) [3] 25351 0
3046 - Glenroy
Recruitment postcode(s) [4] 25352 0
3020 - Sunshine
Recruitment postcode(s) [5] 25353 0
3030 - Werribee
Recruitment postcode(s) [6] 36291 0
2550 - Bega
Recruitment postcode(s) [7] 36292 0
2500 - Wollongong
Recruitment postcode(s) [8] 36293 0
2580 - Goulburn
Recruitment postcode(s) [9] 36294 0
2541 - Nowra
Recruitment postcode(s) [10] 39171 0
2022 - Bondi Junction

Funding & Sponsors
Funding source category [1] 301507 0
Government body
Name [1] 301507 0
National Health and Medical Research Council
Country [1] 301507 0
Australia
Primary sponsor type
Other
Name
Orygen
Address
35 Poplar Rd, Parkville, VIC, 3052
Country
Australia
Secondary sponsor category [1] 303883 0
None
Name [1] 303883 0
Address [1] 303883 0
Country [1] 303883 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302247 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 302247 0
Ethics committee country [1] 302247 0
Australia
Date submitted for ethics approval [1] 302247 0
29/10/2018
Approval date [1] 302247 0
21/02/2019
Ethics approval number [1] 302247 0
HREC/42967/MH-2018

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89574 0
Prof Mario Alvarez-Jimenez
Address 89574 0
Orygen, 35 Poplar Rd Parkville VIC 3052
Country 89574 0
Australia
Phone 89574 0
+61 0401 772 668
Fax 89574 0
Email 89574 0
[email protected]
Contact person for public queries
Name 89575 0
Daniela Cagliarini
Address 89575 0
Orygen, 35 Poplar Rd Parkville VIC 3052
Country 89575 0
Australia
Phone 89575 0
+61 0408 607 919
Fax 89575 0
Email 89575 0
[email protected]
Contact person for scientific queries
Name 89576 0
Daniela Cagliarini
Address 89576 0
Orygen, 35 Poplar Rd Parkville VIC 3052
Country 89576 0
Australia
Phone 89576 0
+61 0408 607 919
Fax 89576 0
Email 89576 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 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.TypeCitationLinkEmailOther DetailsAttachment
4648Study protocol  [email protected]
4650Statistical analysis plan  [email protected]
4651Informed consent form  [email protected]



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