Advancing Precision Medicine for Cardiovascular Disease and Diabetes in Asian Populations: Digital Intervention Cohort

Overview

The overarching aim is to improve cardiometabolic health and promote healthy ageing by supporting adults to adopt favourable lifestyle patterns identified through our observational research. The trial will recruit n=600 to be involved in Phase I (referred to as the "Optimisation Phase") of a two-phase project (Phase II trial registration will be submitted separately). All participants will complete a baseline study visit where, after consent taking, will complete a baseline questionnaire, receive a smartwatch each and additional wearables if applicable, and download the study app for the receiving and testing of interventions and completion of short form surveys. Participants will be involved in the continual evaluation and optimisation of ecological momentary interventions (EMIs) in adaptive, factorial, micro-randomised trials over 12 months. Consenting participants may also be contacted to participate in interviews to be involved in the co-design of interventions, or to provide insights to the feasibility and process evaluation of the trial.

The study adopts a hybrid design among free-living participants, combining an observational study phase with intervention development, testing, optimisation, and evaluation. The trial will recruit n=600 in Phase I (referred to as the "Optimisation Phase"). Optimisation Phase participants are involved in the continual evaluation and optimisation of ecological momentary interventions (EMIs) in adaptive, factorial, micro-randomised trials over 12 months. Participants who are eligible and interested will complete the consent taking, questionnaire, administration of devices (and instructions for removal, where applicable), and app onboarding for COBRA+ study (also known as The Healthy Habits Study). Consent taking (taken face to face and recorded and acknowledged electronically), questionnaire, administration of devices (and instructions for removal, where applicable), and app onboarding would be completed in 2 to 3 hours. Informed consent to participate in the present study will be obtained in a private space. Self-administered questionnaires on personal characteristics and cognitions including personality, habit strength, screen use, typical social and environmental contexts for eating and physical activity, subjective health status, psychosocial and quality of life, work productivity and activity impairment, and healthcare use will be administered. Continuous glucose monitoring (CGM): All participants who do not have a known sensitivity to medical-grade adhesives or a bleeding disorder will be fitted with a CGM sensor (BUZUD CGM 2.0 sensor) on the upper part of their non-dominant arm during the study visit, which they will wear continuously for up to 15 days at a time. These participants will be required to download the BUZUD application ("app") and scan their sensor at least once a day, to share their data with the research team over the study period. They will also receive up to three CGM sensors and applicators in batches (during the in-person visit or via tracked mail) for remote self-administration over the study period. A research team member will remain contactable to provide technical advice, and participants will be offered the option to have the sensor applied by the study operations team at the study site. The CGM product is designed to be minimally invasive, comfortable, and supports self-application; product information for the CGM sensor has been supplemented under the 'Use of Devices' section. Research/operations team may reach out to the participants to verify that the remote application has been administered correctly to avoid fraudulence. Participants will be provided with information on who to contact in the event of experiencing bruising, discomfort, and/or inconvenience when wearing the sensor, and will be directed to contact the operations team via telephone or email to discuss. Smartwatch: All participants will receive a Garmin vivoactive 5 smartwatch to be worn daily over the 12-month study period, and download the Garmin Connect app to support data sharing with the research team. Continuous blood pressure monitor: All participants who do not have contraindications specified by the manufacturer will receive a Huawei D2 smartwatch used to continuously monitor blood pressure, and download the Huawei Connect: Global app to support data sharing with the research team. Participants are required to wear the device daily for 2 weeks from their first study visit. All blood pressure monitors are to be delinked from the participants' smartphones (guided by the Operations Team) and returned at the end of the stipulated wear period to facilitate re-issuance of the device to other participants in-person or using the return enveloped with prepaid postage and tracking number provided with the issuance of the device. Smartphone app: Participants will then be guided through downloading a smartphone-based research app (360INSIGHTS) via the Google Play Store or Apple App Store, and grant the app permission to passively retrieve smartphone-based sensor information related to activity, environmental exposures, and location. Given that these data are collected in the background, no user input is required, imposing minimal burden on the participant despite the extensive and comprehensive list of variables assessed: 1. Device Usage: A sensor that provides information about device usage, such as frequency and duration of device and app usage, notification data, and charging data. Excludes specific names of websites and apps, and content of notifications. 2. Accelerometer: A sensor that provides acceleration motion data 3. Media Events: A sensor that provides information about interactions with media, such as images and videos, in messaging apps. 4. Pedometer: A sensor that provides information about the user's steps. 5. Ambient Light: A sensor that provides ambient light information. 6. Global positioning system (GPS): This data source measures the precise location of the device using GPS sources. A trained interviewer will demonstrate how to use the research app and the participant will have a chance to ask questions. Participants will receive app notifications to complete five-minute, time-triggered EMA surveys via the app up to six times per day over a maximum of ten consecutive days (or "rounds"), with ten EMA rounds over the study period, in which they will be asked about their behaviours (i.e., physical activity, diet) and their physical and social environment. Participants will be randomised to receive EMIs that support the uptake of healthy lifestyle behaviours via the app over 12 months. These EMIs are designed to be engaged with quickly, in the context of daily life, targeting specific behaviours (sleep, diet, and physical activity) over up to four weeks using app- and smartwatch-based content and push notifications. Interviews: A subset of participants who consented to be interviewed will be invited to take part in the co-design process or feasibility study. They will be interviewed in-person at SSHSPH premises or online either in small groups or individually (subject to participant and interviewer availability) by a member of the research team, each session up to 60 minutes. The co-design interviews will be conducted at various stages of the Optimisation Phase to gather the perspectives of end-users among our target population to create practical, relevant, and context-specific interventions that are more likely to be used and owned by our target audience. The feasibility study will be conducted among participants of the Optimisation Phase who were onboarded towards the end of the Optimisation Phase, as they would have tested advanced iterations of the digital intervention. The feasibility study seeks to inform us of the intervention's practicality, acceptability, and potential success, and implementation strategies. All interviews will be audio (and video recorded if conducted online) and stored securely on the servers. Once transcribed verbatim (using Microsoft Office tools), the video and audio files will be deleted. Throughout the trial, should participants experience technical or discomfort issues with the wearables and/or the app, they may contact the researchers via the study phone number provided during the study visit and in-app, who will try to address their concerns over email, WhatsApp, text messaging (SMS) or phone call. For issues that cannot be resolved remotely, participants will be asked to meet researchers at the study site. Adverse events (e.g., bleeding upon initial insertion of the CGM sensor, pain, bruising and bleeding when blood is collected, remote chance of infection and fainting due to blood-taking) are immediately brought to a team member who is a certified first aider for appropriate advice. To mitigate loss of devices and ensure data integrity, we implemented safeguards by mailing CGM sensors in batches; should participants be identified to not adhere to sensor application, a member of the operations team will reach out to lend support, advise on the study procedures, and ascertain safety to proceed. If the participant is uncontactable or refuses to continue applying the CGM sensors, they will not receive further batches of CGM sensors. For the smartwatches and continuous blood pressure monitoring device, should participants be identified to not adhere to recommended wear times, a member of the operations team will reach out to lend support and advise on the study procedures. If the participant is uncontactable, we will regard the device as stolen property of NUS and make reports accordingly to the relevant authorities and/or device company (e.g., Garmin) to block the pairing of the smartwatch with other devices or re-registering of the device under a different account (e.g., if smartwatches are loaned, transferred, or sold to others). Prior to the main study (detailed above), the study investigators will conduct a pilot study among a small sample of up to 50 participants to evaluate recruitment rate, response rate, and overall feasibility of the study methodology. The pilot trial replicates the Optimisation Phase and employs similar procedures, over a shorter duration (3 months). Participants will be recruited based on convenience sampling, who will undergo consent taking, questionnaire, administration of devices (and instructions for removal, where applicable), and app onboarding (2 to 3 hours). Informed consent will be obtained in a private space. All participants will receive the smartwatch and study app, and may receive up to two CGM sensors (if eligible) and the continuous blood pressure monitor device. They will undergo up to 2 EMA rounds, receive EMIs to be tested, and remote CGM and blood pressure monitoring (if applicable). Given that it is a pilot study, all devices issued for pilot trial participants are to be returned in-person or via a return envelope with prepaid postage and tracking number provided together with the issuance of the devices. A subset of pilot study participants who consented to be interviewed will be invited to take part in the feasibility interview (up to n=30) after they have been enrolled for at least 1 month into the study. They will be interviewed in-person or online either in small groups or individually (subject to participant and interviewer availability) by a member of the research team, each session up to 60 minutes. There is no follow-up visit for pilot trial participants.