Advancing Precision Medicine for Cardiovascular Disease and Diabetes in Asian Populations: Digital Intervention Cohort (COBRA+)

Advancing Precision Medicine for Cardiovascular Disease and Diabetes in Asian Populations: Digital Intervention Cohort (COBRA+)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Physical Activity; Sleep; Diet Quality; Cardiometabolic Health; Digital Intervention
• Intervention / Treatment: Behavioral: Lifestyle intervention targeting physical activity, sleep, and diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Yi Xuan Tan, PhD; Phone Number: +65 65164988; Email: sarah.tan@nus.edu.sg

Study Locations

• Singapore
  • Singapore, Singapore, 117549
    • Saw Swee Hock School of Public Health
    • Contact: Sarah Yi Xuan Tan, PhD; Phone Number: +65 65164988; Email: sarah.tan@nus.edu.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• are currently enrolled in the Singapore Population Health Studies - Multi-Ethnic Cohort Phase 3 (MEC3) or Second Follow-up (F2),
• are of Chinese, Malay, or Indian ethnicity,
• are 21 to 69 years old, and
• can read and write English,
• own or use a smartphone (iOS ≥ 12.4 or Android ≥ 8 with at least 5 GB of free storage, and data plan and internet access),
• are able and willing to download and use study smartphone apps,
• are able and willing to wear the smartwatch provided throughout the study period, and
• can walk independently.

Exclusion Criteria:

• have a history or current condition of stroke, heart attack, kidney failure, diabetes mellitus, thyroid disease, or cancer, or have had a vascular bypass surgery or angioplasty procedure (either stent or balloon) performed, or
• a serious mental health condition including schizophrenia, psychotic depression, or severe dementia, or
• are currently pregnant or planning to get pregnant during the study period, or
• are participating or planning to participate in other lifestyle intervention studies.
• have a known sensitivity to medical-grade adhesives or a bleeding disorder will be [applicable to continuous glucose monitoring component only]
• with contraindications specified by the blood pressure monitoring device manufacturer [applicable to continuous blood pressure monitoring component only]
• participated in the pilot study [applicable to main trial only].

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Pure Control Arm; Participants receive the control (no intervention) version for both factors (Factor A control + Factor B control)
Experimental: Active/Control Arm; e.g., in a physical activity (Factor A) x diet (Factor B) (2 x 2) factor, participants in this arm received only the physical activity intervention	Behavioral: Lifestyle intervention targeting physical activity, sleep, and diet; Ecological momentary interventions targeting physical activity, sleep, and diet
Experimental: Control/Active Arm; e.g., in a physical activity (Factor A) x diet (Factor B) (2 x 2) factor, participants in this arm received only the diet intervention	Behavioral: Lifestyle intervention targeting physical activity, sleep, and diet; Ecological momentary interventions targeting physical activity, sleep, and diet
Experimental: Active/Active arm; e.g., in a physical activity (Factor A) x diet (Factor B) (2 x 2) factor, participants in this arm received both the physical activity and diet intervention	Behavioral: Lifestyle intervention targeting physical activity, sleep, and diet; Ecological momentary interventions targeting physical activity, sleep, and diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants having sufficient physical activity	Based on self-report and devices	At baseline, and every 5 weeks, up to 52 weeks from joining the study
Number of participants having sufficient sleep	Based on self-report and devices	At baseline, and every 5 weeks, up to 52 weeks from joining the study
Number of participants meeting dietary guidelines	Based on self-report	At baseline, and every 5 weeks, up to 52 weeks from joining the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycaemic response	Measured using continuous glucose monitors	Up to 3 assessments in total, each assessment lasting 2 weeks, with all assessments completed within 52 weeks from joining the study

Collaborators and Investigators

• Sponsor: National University of Singapore
• Investigators: Principal Investigator: Falk Müller-Riemenschneid, PhD, National University of Singapore

Study record dates

Study Major Dates

• Study Start (Estimated): July 20, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2031

Study Registration Dates

• First Submitted: July 10, 2026
• First Submitted That Met QC Criteria: July 23, 2026
• First Posted (Actual): July 27, 2026

Study Record Updates

• Last Update Posted (Actual): July 27, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: smartphone; mHealth; intervention; digital health; ecological momentary assessment; EMA; smartwatch; ecological momentary intervention; EMI; microrandomised trial
• Additional Relevant MeSH Terms: Behavior; Motor Activity; Musculoskeletal and Neural Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Nervous System Physiological Phenomena; Diet; Sleep
• Other Study ID Numbers: NUS-IRB-2025-817

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No