UMIN-CTR Clinical Trial

Public title

BEATRICE (Best, Efficient and Affordable Training in Resilience In Constant Evolution) Platform Trial

Acronym

BEATRICE Platform Trial

Scientific Title

BEATRICE (Best, Efficient and Affordable Training in Resilience In Constant Evolution) Platform Trial

Scientific Title:Acronym

BEATRICE Platform Trial

Region

Japan

Condition

Adults with no to mild (subthreshold) depressive sypmtoms

Classification by specialty

Psychiatry

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The overarching aim of this platform trial is to minimize the cumulative burden of depressive symptoms, measured as the sum of weekly to monthly PHQ-8 scores over 12 months, through a series of randomised investigations targeting the following clinical questions (CQ).
CQ1. External validity of the personalised & optimised therapy (POT) algorithm for first-line interventions, developed from the RESiLIENT trial data (Furukawa et al, submitted)
CQ2. Strategies to help individuals not on track (NOT) during initial weeks of intervention,
CQ3. Second-line interventions at 6 months,
CQ4. Development of the super-personalised & optimised therapy (SPOT) algorithm based on longitudinal data,
CQ5. Encouragement messages via LINE (a widely used instant messaging app in Japan, similar to WhatsApp) to improve adherence to the app
CQ6. Financial incentives to promote the uptake of the app in the population
CQ7. Refinement of the POT algorithm for specific populations (e.g., new employees, factory workers, highly skilled brain workers, healthcare workers),
CQ8. Added value of cognitive restructuring for BI.

The BEATRICE platform is a living RCT capable of addressing new clinical questions and accommodating future refinements by leveraging rapid and as-yet-unforeseen technological advances, such as the use of generative AI to guide users through cognitive restructuring and problem-solving worksheets.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Others

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

The primary outcomes differ depending on the clinical question addressed within the platform trial. In most cases, they involve depressive symptom severity measured by the Patient Health Questionnaire-8 (PHQ-8). Specific metrics include:

CQ1 (First-line interventions): Change in PHQ-8 scores from baseline (Week 0) to Week 26.
CQ2 (NOT interventions): Change in PHQ-8 scores from Week 2 to Week 26
CQ3 (Second-line interventions): Change from Week 26 to Week 52
CQ4 (SPOT algorithm): Total Burden of Depression (TBD), which is calculated as the integral of PHQ-8 scores over 52 weeks.
CQ5 (Encouragement LINE): Change in PHQ-8 scores from baseline (Week 0) to Week 26.
CQ6 (Incentives): Proportion of randomised participants out of those approached.
CQ7 (POT algorithm for subgroups): Change in PHQ-8 scores from baseline (Week 0) to Week 26.
CQ8 (New BI module): Change in PHQ-8 scores from baseline (Week 0) to Week 26 or from Week 26 to Week 52.

Key secondary outcomes

Secondary Outcomes
We will analyse the following secondary outcomes to supplement and expand the interpretation of the primary outcomes. The statistical analysis plan for each CQ will detail how to analyse these outcomes.

Changes in PHQ-8 from baseline to Weeks 2, 3, 4, 5, 6, 10, 14, 18, 22, 26, 27, 28, 29, 30, 31, 32, 36, 40, 44, 48, 52
Changes in Insomnia Severity Index (ISI) from baseline to Weeks 3, 6, 26, 29, 32, and 52.
Changes in Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS) from baseline to Weeks 3, 6, 26, 29, 32, and 52.


Tertiary Outcomes
We will conduct exploratory analyses of the following outcomes in order to describe the changes in the BEATRICE platform in a multifaceted way.

Onset of a major depressive episode as diagnosed with the CIDI.
Changes in social function, work engagement, presenteeism, health utility and medical expenditures from baseline to Weeks 6, 26, 32, 52.
Change in cognitive-behavioural skills from baseline to Weeks 26, and 52.
Changes in premenstrual mental symptoms (PMS-8) from baseline to Weeks 26 and 52.
Satisfaction with the intervention (Customer Satisfaction Questionnare-3, CSQ-3), app usage, concomitant treatments, and adverse events

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

10

Purpose of intervention

Educational,Counseling,Training

Type of intervention

Other

Interventions/Control_1

CQ2: We will randomise those judged NOT at week 2 to the following NOT interventions or the control condition in equal proportions.
1. Motivational Interviewing-based prompts

Interventions/Control_2

CQ2: We will randomise those judged NOT at week 2 to the following NOT interventions or the control condition in equal proportions.
2. Proposal to take a break

Interventions/Control_3

CQ2: We will randomise those judged NOT at week 2 to the following NOT interventions or the control condition in equal proportions.
3. Proposal to learn an alternative module (Among those with baseline PHQ-8<=4, we will propose BA for those who started with AT or BI and CR for those who started with BA+CR. Among those with baseline PHQ-8>=5, we will propose the second module as if it were an alternative module to encourage a fresh start.)

Interventions/Control_4

CQ2: We will randomise those judged NOT at week 2 to the following NOT interventions or the control condition in equal proportions.
4. No additional intervention

Interventions/Control_5

CQ3: Stratified by the PHQ-8 scores =4 or >=5 at week 26, we will randomise and compare the following four interventions at week 26.
1. The therapy with the highest PrBest based on the POT algorithm on the Week 26 (and 28) data; when this is the same as their first-line therapy, the therapy with the second highest PrBest.

Interventions/Control_6

CQ3: Stratified by the PHQ-8 scores =4 or >=5 at week 26, we will randomise and compare the following four interventions at week 26.
2. Review of the first-line therapy

Interventions/Control_7

CQ3: Stratified by the PHQ-8 scores =4 or >=5 at week 26, we will randomise and compare the following four interventions at week 26.
3. User's choice (We will ask the participant to pick up one skill to learn, after all five skills have been explained.)

Interventions/Control_8

CQ3: Stratified by the PHQ-8 scores =4 or >=5 at week 26, we will randomise and compare the following four interventions at week 26.
4. No second-line therapy

Interventions/Control_9

CQ5: To determine the optimal level of human involvement, we will compare the following three approaches using 1:1:1 individual randomisation:
1. Full human encouragement: The CRC is identified and introduced to the participant. Personalised manually-delivered messages plus manual responses when the participants respond to the messages through the six weeks of the intervention (including technical support).
2. Partial human involvement : The CRC is identified and introduced to the participant. However, all messages are automated. The CRC responds manually when the participants respond to the messages. The latter will involve technical support.
3. Fully automated: The CRC is not personally identified. All messages are fixed messages and no human involvement. Only technical support is provided by humans.

Interventions/Control_10

CQ6: We will compare the following three compensation conditions on the BEATRICE platform using cluster randomisation in a 1:1:1 allocation. They fall within the range of incentives that health insurance associations or companies currently provide for their health promotion activities.
1. Total of 3,000 yen in Amazon gift cards (500 yen at Week 6, 1000 yen at Week 26, 500 yen at Week 32, 1000 yen at Week 52)
2. Total of 600 yen in Amazon gift cards (100 yen at Week 6, 200 yen at Week 26, 100 yen at Week 32, 200 yen at Week 52)
3. No compensation

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Inclusion criteria:
- Individuals aged 18 years or older at the time of consent.
- Ownership of a personal smartphone (iPhone or Android).
- Provision of informed electronic consent to participate in the study.
- A PHQ-8 total score of 14 or less at screening.
- Completion of the second part of the baseline questionnaire and completion of the app's introductory lesson ("Getting Started") within one week of initiating the screening survey.

Key exclusion criteria

Exclusion criteria:
- Inability to read or understand Japanese.
- Current treatment for a mental health condition at the time of screening.

Target sample size

42000

Name of lead principal investigator

1st name	Toshiaki
Middle name
Last name	Furukawa

Organization

Kyoto University

Division name

Office of Institutional Advancement and Communications

Zip code

6068601

Address

Yoshida Konoe-cho, Sakyo-ku, Kyoto

TEL

0757539491

Email

toshi.a.furukawa@gmail.com

Name of contact person

1st name	Toshiaki
Middle name
Last name	Furukawa

Organization

Kyoto University

Division name

Office of Institutional Advancement and Communications

Zip code

6068501

Address

Yoshida Konoe-cho, Sakyo-ku, Kyoto

TEL

0757539491

Homepage URL

Email

toshi.a.furukawa@gmail.com

Institute

Kyoto University

Institute

Department

Personal name

Toshiaki Furukawa

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kyoto University Graduate School of Medicine Ethics Committee

Address

Shogoin Kawahara-cho 53, Sakyo-ku, Kyoto

Tel

075-366-7618

Email

ethcom@kuhp.kyoto-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2025

Year

11

Month

01

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2025

Year

08

Month

05

Day

Date of IRB

Anticipated trial start date

2025

Year

11

Month

01

Day

Last follow-up date

2029

Year

05

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2025

Year

08

Month

05

Day

Last modified on

2025

Year

10

Month

29

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000067053