Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001272684
Ethics application status
Approved
Date submitted
7/11/2023
Date registered
7/12/2023
Date last updated
23/05/2024
Date data sharing statement initially provided
7/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluating the use of digitally enhanced treatment models in early intervention for youth with bipolar disorder.
Scientific title
A randomised-control trial evaluating the effectiveness of a novel, multi-component model of care for youth with Bipolar Disorder I or II.
Secondary ID [1] 310773 0
Sponsor Protocol Number: ORY-P12-20-19
Universal Trial Number (UTN)
Trial acronym
BLEND-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bipolar Disorder 331733 0
Condition category
Condition code
Mental Health 328480 328480 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BLEND:
BipoLar Early intervention using New Digital technologies (BLEND) is a multi-component, blended digital model of care designed to improve symptomatic outcomes for youth in the early course of BD. This model combines (i) evidence-based pharmacotherapies for acute and maintenance treatment of BD, (ii) psychological therapy for BD delivered through in-person individual therapy sessions blended with digital intervention content, as well as (iii) a digitally supported relapse monitoring strategy, in addition to routine care.

(i) Evidence based and tolerable pharmacotherapies delivered in a shared decision making paradigm: This component includes psychiatrists offering evidence based recommendations for acute and maintenance treatment in bipolar disorder in 2-4 sessions over 8 months using a shared decision making paradigm. In the BLEND arm, psychiatrists will recommend the use of newer and more tolerable atypical medications such as lurasidone and aripiprazole, in addition to TGA approved and PBS subsidized guideline concordant medications.

(ii) Blended psychological therapy includes both in-person psychological therapy as well as digital psychological interventions targeting bipolar disorder. For each young person, a clinical psychologist/mental health clinician will provide manualised and formulation driven cognitive behaviourally informed therapy based on a locally developed intervention for young people experiencing bipolar disorder. The therapist will also facilitate engagement with digital psychological therapy content (embedded within and accessed through blend.most digital platform) in a blended manner. Participants in the BLEND arm will also have access to modules targeting psychoeducation for Bipolar Disorder, preventing relapses and social rhythm therapy. Interventions will be delivered via 10-14 (50-60min) face-to-face sessions, over 8 months. Treatment fidelity will be achieved by completion of therapy fidelity checklists and regular clinical supervision.

(iii) Digitally supported relapse monitoring: Those in BLEND will also receive access to a weekly self-rating tool implemented within the MOST platform which includes a) the Altman Self-Rated Mania Scale, b) items from the Quick Inventory of Depressive Symptomatology, and c) self-assessment of need for additional care. This weekly self-rating tool is supported by SMS prompts, and responses will be forwarded to BLEND clinicians able to respond via established relapse prevention plans.

Routine care includes
1) Needs based interventions to respond to acuity or changes in risk. This may include (i) Additional appointments with a psychiatrist, therapist, or peer support worker, (ii) Additional phone check-in/monitoring from therapist or peer support worker, or (iii) Changes to medication.

2) Access to Moderated Online Social Therapy (MOST): The MOST platform is an interactive, purpose-built, online platform designed to deliver a range of evidence-based and interactive psychosocial interventions. The modules targeting depression, anxiety, social functioning, and vocational functioning are available for all young people irrespective of whether they are in BLEND or Enhanced Standard Care. The platform also includes an online social networking environment, which is moderated by peer support workers. Participants are able to access psychosocial interventions on MOST 24-hours per day, 7 days per week from any internet-enabled device for the 6 months of the study period.

3) Peer Support interventions: Participants in both arms have access to dedicated peer support workers through the MOST platform. They can message peer support workers, engage with them through posts online, or organise telephone contact.

Pharmacotherapeutic interventions will be monitored through regular appointments with psychiatrists and research assistants. Psychiatrists will monitor self-reported efficacy, , tolerability, and medication adherence, documenting these details in the medical record. Every two months, participants will complete assessments with research assistants. Prior to assessments, RAs will check medical/trial records to identify current prescribed trial medications. RAs will then in each appointment assess the participant’s use of each prescribed medication including (i) how many times a prescription has been filled, (ii) batch numbers for each prescription filled, (iii) frequency of having missed prescribed medication, and (iv) duration of taking each medication at each dose. Finally, Attitudes and behaviour related to medication adherence are also captured through the self-report measure Medication Adherence-Rating Scale (MARS) which is administered at Baseline and 2,4,6,8,10 and 12-months post-Baseline assessment.
Intervention code [1] 327249 0
Treatment: Other
Comparator / control treatment
BLEND will be compared to an enhanced form of standard care (ESC). ESC includes similar elements of care such as pharmacological interventions, psychological interventions, access to digital psychological therapy content and peer work sessions, in addition to routine care.

Psychopharmacological interventions: For ESC participants, psychiatrists will provide evidence based recommendations for guideline concordant, TGA approved and PBS subsidized in Australia, in 2-4 sessions within 8-months utilising shared decision making principles.

Psychological interventions: ESC participants will receive up to 10 appointments of psychological therapy (50-60 minutes each). Therapy will be based upon a locally developed Brief Interventions in Youth Mental Health (BIYMH) toolkit. The BIYMH toolkit reflected needs-based cognitive-behaviour therapy available in the community and comprises 9 modules from which to create a participant-specific treatment plan including: assertiveness, anger management, physical activity, treatment for low mood and anxiety, problem solving skills, mindfulness/relaxation, self-compassion, sleep, and nutrition.

Peer support work: Peer support workers have greater involvement with ESC participants, who have access to up to 4 in-person appointments with peer support workers over the course of the study, in addition to access to peer support workers through the MOST platform.

Routine care includes
1) Needs based interventions to respond to acuity or changes in risk. This may include (i) Additional appointments with a psychiatrist, therapist, or peer support worker, (ii) Additional phone check-in/monitoring from therapist or peer support worker, or (iii) Changes to medication.

2) Access to Moderated Online Social Therapy (MOST): The MOST platform is an interactive, purpose-built, online platform designed to deliver a range of evidence-based and interactive psychosocial interventions. The modules targeting depression, anxiety, social functioning, and vocational functioning are available for all young people irrespective of whether they are in BLEND or Enhanced Standard Care. The platform also includes an online social networking environment, which is moderated by peer support workers. Participants are able to access psychosocial interventions on MOST 24-hours per day, 7 days per week from any internet-enabled device for the 6 months of the study period.

3) Peer Support interventions: Participants in both arms have access to dedicated peer support workers through the MOST platform. They can message peer support workers, engage with them through posts online, or organise telephone contact.
Control group
Active

Outcomes
Primary outcome [1] 336302 0
The proportion of weeks in threshold mood episodes (either depressed, hypomanic, or a combination of both) over the 16-week period preceding the assessment.
Timepoint [1] 336302 0
Baseline and 2, 4, 6, 8, 10, 12 months from Baseline. Primary end-point is the end-of-treatment assessment at 8-months from Baseline.
Secondary outcome [1] 427771 0
Self-reported quality of life
Timepoint [1] 427771 0
Baseline and 2, 4, 6, 8, 10, 12 months from Baseline.
Secondary outcome [2] 428512 0
Overall Bipolar Illness Severity
Timepoint [2] 428512 0
Baseline and 2, 4, 6, 8, 12 months from Baseline.
Secondary outcome [3] 428513 0
Time to relapse
Timepoint [3] 428513 0
Baseline and 2, 4, 6, 8, 10, 12 months from Baseline.
Secondary outcome [4] 428514 0
Bipolar Self-Efficacy
Timepoint [4] 428514 0
Baseline, 4, and 8-months from Baseline.
Secondary outcome [5] 428515 0
Socio-occupational function
Timepoint [5] 428515 0
Baseline and, 2, 4, 6, 8, 10, and 12 months from Baseline.
Secondary outcome [6] 428516 0
Sleep Quality
Timepoint [6] 428516 0
Baseline, 4, and 8-months from Baseline.
Secondary outcome [7] 428517 0
Self-reported (Hypo)manic Symptoms
Timepoint [7] 428517 0
Baseline and, 2, 4, 6, 8-months from Baseline.
Secondary outcome [8] 428518 0
Self-reported Depression Symptoms
Timepoint [8] 428518 0
Baseline and, 2, 4, 6, 8-months from Baseline.
Secondary outcome [9] 428519 0
Cost-effectiveness of the BLEND Model
Timepoint [9] 428519 0
RUQ: Baseline and, 4, 8, 12-months from Baseline.
Secondary outcome [10] 428520 0
Anxiety symptoms
Timepoint [10] 428520 0
Baseline and, 2, 4, 6, 8-months from Baseline.
Secondary outcome [11] 428521 0
Patient impressions of improvement
Timepoint [11] 428521 0
2, 4, 6, 8, 10, 12-months from Baseline.
Secondary outcome [12] 428523 0
Suicidality
Timepoint [12] 428523 0
Baseline and, 2,4, 6, 8-months from Baseline.
Secondary outcome [13] 428525 0
Service use 5-years use post-discharge: Time to first inpatient/outpatient contact for mental or physical health complaints
Timepoint [13] 428525 0
0 to 5-years post-discharge
Secondary outcome [14] 429121 0
Interviewer-rated (Hypo)manic Symptoms
Timepoint [14] 429121 0
Baseline and 2,4,6,8,10, and 12-months from Baseline
Secondary outcome [15] 429122 0
Interviewer-rated Depression Symptoms
Timepoint [15] 429122 0
Baseline and 2,4,6,8,10,and 12-months from Baseline
Secondary outcome [16] 429123 0
Service use 5-years use post-discharge: Number and type of inpatient admissions or outpatient contacts for mental or physical health complaints
Timepoint [16] 429123 0
0 to 5-years post-discharge
Secondary outcome [17] 429125 0
Service use 5-years use post-discharge: Any review of diagnosis.
Timepoint [17] 429125 0
0 to 5-years post-discharge

Eligibility
Key inclusion criteria
1. Age 15 to 25 years.
2. Diagnosis of BD I or II.
3. Ability to provide informed consent and/or have a parent or guardian provide consent on their behalf.
4. Ability and willingness to nominate an emergency contact person, such as a close family member.
Minimum age
15 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has previously received 6-months of tertiary care through a mental health service or multi-disciplinary team for bipolar disorder or psychosis.
2. Currently requiring more than weekly clinical contact (for 4 weeks or more) or likely to require at least weekly clinical contact (for 4 weeks or more) in the next 6-months, due to high level of severity, complexity, or risk.
3. Experiencing psychosis or manic episode*
4. Intellectual disability that interferes with the likelihood of the participant receiving benefit from participation as judged by the treating clinician.
5. Inability to converse in or read English. English does not have to be the young person’s primary language.
6. Does not have access to the internet and an internet-enabled device.
7. High degree of hostility and impulsivity, as judged by the treating clinician, resulting in the clinician believing that inclusion in the research project may result in harm to the young person or other users (i.e., through interactions in the social network).
8. Has a schizophrenia spectrum diagnosis or a significant primary mental disorder that requires a different model of care, as determined by the clinical team.

*Those experiencing a (hypo)manic episode will be offered treatment, and upon remission, can be admitted to the study if they meet other eligibility criteria.

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 computer-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 based on a permutated block randomisation scheme with stratification for gender and bipolar disorder types I or II.
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
Efficacy
Statistical methods / analysis
Sample-size estimation: Given the importance of Minimum Clinically Important Differences (MCID) in estimating target effect size of group differences particularly for patient reported outcomes, we utilised MCID between groups of 1.8 weeks spent in any mood episode. MCID was based on clinical judgment of clinicians from the BLEND pilot trial, as well as data from the pilot trial. Combined with variances (SD equals 3.46) from the BLEND pilot trial for LIFE, we arrived at a target effect size of eta-squared equal to 0.08, equivalent to a standardised regression coefficient of 0.52.

Based on this effect size, an alpha of .05, power set at 0.80, and one set of covariates which account for 20 percent of the variance on the primary outcome (e.g., baseline measurements, stratification variables), we would require a total of 96 participants. To allow for an attrition rate of 30% (based on our previous studies), we would need to recruit a total of 125.

Main analysis: Linear-mixed effects regression adjusting for baseline measurements of the outcome and variables used for stratification.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
1/11/2027
Actual
Date of last data collection
Anticipated
1/11/2033
Actual
Sample size
Target
125
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25771 0
Orygen Youth Health - Parkville - Parkville
Recruitment postcode(s) [1] 41596 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 315003 0
Government body
Name [1] 315003 0
National Health and Medical Research Council
Country [1] 315003 0
Australia
Funding source category [2] 315086 0
Government body
Name [2] 315086 0
VIC Department of Health
Country [2] 315086 0
Australia
Funding source category [3] 315087 0
Charities/Societies/Foundations
Name [3] 315087 0
Orygen
Country [3] 315087 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Orygen
Address
35 Poplar Rd, Parkville, VIC, 3052
Country
Australia
Secondary sponsor category [1] 317110 0
None
Name [1] 317110 0
N/A
Address [1] 317110 0
N/A
Country [1] 317110 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313975 0
Royal Melbourne Hospital Human Research and Ethics Committee
Ethics committee address [1] 313975 0
The RMH Parkville, Level 2 South West, 300 Grattan St, Parkville, VIC 3052
Ethics committee country [1] 313975 0
Australia
Date submitted for ethics approval [1] 313975 0
26/09/2023
Approval date [1] 313975 0
08/03/2024
Ethics approval number [1] 313975 0
2023.173

Summary
Brief summary
Currently, specialised early interventions are not accessible for a majority of youth with Bipolar Disorder (BD) who seek care. To address this gap, we have developed a bipolar-specific model of care for those with early-stage BD (BLEND) integrating: (i) evidence-based psychological strategies delivered through digital and face-to-face sessions; (ii) psychopharmacological interventions; (iii) relapse prevention strategies, and (iv) online peer support networking. We will conduct a randomised trial to evaluate the effectiviness of BLEND, compared with an enhanced form of standard care (ESC). We will include young people aged between 15 and 25 years, seeking specialised help for Bipolar Disorder types I or II. After informed consent, we will randomise 125 such young people (1:1) to BLEND or ESC. Interventions will be delivered over 8 months and assessments will be conducted at Baseline, 2, 4, 6, 8, 10, and 12 months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129986 0
Dr Aswin Ratheesh
Address 129986 0
Orygen, 35 Poplar Rd, Parkville, VIC, 3052
Country 129986 0
Australia
Phone 129986 0
+61 03 9966 9207
Fax 129986 0
Email 129986 0
aswin.ratheesh@orygen.org.au
Contact person for public queries
Name 129987 0
Mr Dylan Hammond
Address 129987 0
Orygen, 35 Poplar Rd, Parkville, VIC, 3052
Country 129987 0
Australia
Phone 129987 0
+61 0401 805 662
Fax 129987 0
Email 129987 0
dylan.hammond@orygen.org.au
Contact person for scientific queries
Name 129988 0
Mr Dylan Hammond
Address 129988 0
Orygen, 35 Poplar Rd, Parkville, VIC, 3052
Country 129988 0
Australia
Phone 129988 0
+61 0401 805 662
Fax 129988 0
Email 129988 0
dylan.hammond@orygen.org.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 available data, de-identified.
When will data be available (start and end dates)?
Data will be available after the main results have been published 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 management 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?

No Supporting Document Provided



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.