Clinical trials

This study examines whether routine treatment with semaglutide or tirzepatide, prescribed with lifestyle coaching in a real-world weight-management program, is associated with changes in biological age measured by the LinAge2 clinical aging clock over 6 months.

Sleep problems are common in adolescents. Studies have consistently demonstrated that sleep disturbances are prevalent, affecting up to 50% of this population. In this project, the investigators aim to map out sleep patterns, risk factors, and obstacles for sleep in adolescents, capturing the diversity of societal factors that shape the sleeping habits of adolescents. The investigators aim to recruit school-aged adolescents (aged 12-18 years old) in 12 countries across 15 research centres (N = 1000 per centre) to fill in the questionnaire covering sleep-wake patterns, sleep problems, mood, behavioral, daytime functioning and their attitude and perception towards sleep.

The goal of this study is to understand how caffeine and alcohol affect the ocular and physiological systems, especially how the pupil (the aperture in the colored part of the eye) responds to light. It will also test whether these changes can be used to detect recent caffeine or alcohol intake using a portable eye device. The main questions it aims to answer are: 1. How does caffeine change pupil responses, eye movements, and other ocular and physiological measurements? 2. How does alcohol change these same ocular and physiological responses? 3. Are the effects of caffeine and alcohol different from each other? 4. Can these changes be used to accurately identify whether someone has consumed caffeine or alcohol? Researchers will compare caffeine, alcohol, and a placebo (a look-alike drink with no active substance) to see how each affects the ocular and physiological outcomes. Participants will: 1. Attend three separate sessions where they will consume caffeine, alcohol, or a placebo (in random order) 2. Undergo pupillary response evaluation using a handheld device that measures responses to different colored light stimuli 3. Have their eye movements analyzed 4. Have retinal and choroidal thickness, blood perfusion, and ocular oxygen levels measured 5. Have basic body measurements recorded (such as pulse rate and blood pressure) 6. Complete tests at multiple time points over 2 hours after consumption The results of this study may help develop a quick and non-invasive way to detect recent caffeine or alcohol use for clinical and safety purposes.

Cognitive-behavioural therapy (CBT) has a robust evidence base for treating anxiety disorders and depression, including transdiagnostic CBT. Internet-based CBT (iCBT) offers a new approach to delivering these therapies. iCBT is a digital adaptation of traditional CBT that leverages digital platforms to deliver similar therapeutic interventions. iCBT encompasses structured programmes that provide users with tools and techniques to manage mental health issues such as depression and anxiety. The digital format ensures timely access to CBT and typically includes interactive modules, videos, self-assessment tools, and virtual therapist support. This study aims to evaluate the effectiveness of iCBT in reducing symptoms of anxiety and depression, as well as its cost-effectiveness and acceptability in local context. The main questions it aims to answer are: 1. Do participants receiving iCBT show a reduction in symptoms of anxiety and/or depression, and does the effectiveness of iCBT vary based on individual user characteristics? 2. What are the factors that influence the acceptance, adoption, and engagement rates of iCBT among Singaporeans? 3. Is iCBT more cost-effective as compared to usual care? Researchers will compare guided iCBT to usual care (traditional CBT) to assess iCBT's clinical effectiveness, cost-effectiveness, and acceptability in Singapore's primary and community healthcare settings. Participants in the intervention group will: 1. Undergo guided iCBT intervention consisting of 8 weeks of online modules covering core CBT techniques 2. Counsellors will schedule 3 regular check-ins 3. Questionnaires will be administered at 5 timepoints 4. Selected participants will be invited for a semi-structured interview to assess their experiences with iCBT Participants in the control group will: 1. Continue usual care 2. Questionnaires will be administered at 5 timepoints A parallel qualitative study involving service providers is required to contextualise trial findings, identify implementation barriers and enablers and inform national scale-up and policy decisions. It aims to explore service providers' experiences, perceptions and contextual factors influencing the implementation of iCBT within routine primary-care and community mental-health services participating in this trial.

Aim: To evaluate the effectiveness of an artificial intelligence (AI)-assisted 12-month Health Coach-Led Digital Lifestyle Intervention (HEALDI) versus control on diffuse myocardial fibrosis and ambulatory blood pressure in individuals with hypertensive heart disease (HHD), with secondary outcomes including multi-organ health parameters, health behaviours, social support, psychological health, and health-related quality of life. Background: The global prevalence of hypertensive heart disease (HHD) has increased approximately 1.5-fold, from 7.82 million cases in 1990 to 12.50 million in 2021, and it is now the second leading cause of heart failure worldwide. In HHD, chronic pressure overload drives fibroblast activation and interstitial collagen deposition, leading to diffuse myocardial fibrosis which is associated with cardiac dysfunction, arrhythmias, impaired coronary flow reserve, and an increased risk of sudden cardiac death and heart failure. Although diffuse myocardial fibrosis is potentially reversible, no approved anti-fibrotic pharmacological therapy currently exists. Furthermore, there is limited evidence evaluating the effectiveness of lifestyle interventions, particularly aerobic exercise, in reversing diffuse myocardial fibrosis. Design: A parallel, single-blinded two-arm randomised controlled trial. Method: This study is a randomised controlled trial with repeated measures, recruiting 200 physically inactive individuals with HHD from the community, including participants from Project RESET, a community-based cohort study in Singapore. Participants will be randomly allocated to either the intervention or control group. Participants in the intervention group will receive the 12-month HEALDI intervention, which includes the HEALDI mobile application, wearable device, and remote health coaching. Participants in the control group will receive a wearable device and a basic mobile application without intervention features, used solely for data collection. Data will be collected at baseline (upon randomisation) and at 6, 12 and 24 months. A process evaluation will be conducted using intervention engagement data. In addition, semi-structured interviews with participants and health coaches will explore perceptions of the intervention and behaviour change. A within-trial economic evaluation, from both healthcare system and societal perspectives, will be performed to assess cost-effectiveness. Significance: This study will generate insights into the role of lifestyle modification as a complementary, non-pharmacological strategy alongside pharmacotherapy to halt or slow HHD progression, improving long-term cardiovascular outcomes.

The goal of this pilot trial is to evaluate the feasibility of a mobile-assisted brief intervention for smoking cessation in community-based individuals in Singapore. Specific aims include: 1. To assess how many eligible individuals accept the invitation to participate in the trial 2. To assess the retention of the participants through 6 months after treatment initiation 3. To assess the acceptability of the intervention in terms of participants' engagement and ratings 4. To examine the intervention effect on abstinence outcomes Participants will be randomly assigned to either the intervention group or control group and followed for 6 months from randomisation.

The investigators aim to investigate the relationship between lifestyle factors and cognitive decline among older Singaporeans and assess the feasibility and preliminary efficacy of a lifestyle intervention programme in delaying cognitive decline. Healthy lifestyle is a way of living that can lower down disease risk and promote health and wellbeing. Accumulating evidences support that lifestyle factors contribute to the development of dementia and hence modifying lifestyle could be a promising approach for dementia prevention. The intervention will focus on the promotion of a brain-healthy lifestyle, with special attention paid to common problems among local older adults. The investigators will assess cognitive and biological changes using the following outcome measures. Primary outcome: the processing speed domain Z score derived from raw scores of three tests including the symbol digit modality test, Colour trial test, and Stroop test (condition 2). Secondary outcome: i. epigenetic age (DNA methylation), ii. plasma-based markers of inflammation, iii. activities of daily living and instrumental activities of daily living, iv. Health-related quality of life measured by the EQ-5D-5L scale, v. wellbeing measured by the ICECAP-O (ICEpop CAPability measure for Older people), vi. other neurocognitive assessment tests. The investigators hypothesize that: 1. Lifestyle factors are associated with cognitive decline, epigenetic age, and systematic chronic inflammation. 2. Evidence-based lifestyle intervention focusing on common problems among local population can delay cognitive decline, slow epigenetic ageing, and produce favorable changes on chronic systemic inflammation. 3. Changes in biological markers will correlate with changes in cognitive function, and hence partially explains the observed clinical efficacy. 4. The interventions may also improve daily functioning, health-related quality of life, and wellbeing. 5. Interventions delivered in an individualized manner would produce more benefits than interventions delivered uniformly without considering individual's risk profile and personal and social context.

The goal of this clinical trial is to evaluate whether the Die-logue program can improve attitudes toward death, coping with death, and readiness for advance care planning (ACP) among community-dwelling middle-aged adults aged 40-60 years who have not completed any advance directives and not diagnosed with any life limiting diseases. This study aims to address the following research questions: * Does the Die-logue program improve community-dwelling middle-aged adults' attitudes towards death, ability to cope with death, readiness and uptake for Advanced Care Planning (ACP). * What are community-dwelling middle-aged adults' perceptions of advance care planning, death and dying, and their experiences of participation in the Die-logue program. Researchers will compare participants who receive the Die-logue program (death conversation and online ACP education) with participants who receive only the online ACP education to see if informal death conversations improve attitudes toward death, coping with death, and readiness for ACP. Participants will: * Complete online questionnaires measuring attitudes toward death, coping with death, and readiness for advance care planning. * Participate in a facilitator-led group discussion session about perceptions of death, coping with death, and readiness for ACP (intervention group only). * Complete an asynchronous online ACP education session consisting of short recorded videos and an online discussion forum (both intervention and control group). * Complete follow-up surveys, including a 6-month follow-up assessing whether they have undertaken advance care planning.

The goal of this pilot trial is to evaluate the feasibility and potential effectiveness of a caregiver-mediated, technology-facilitated home-based intervention named Frailty Improvement through Technology With Informal Caregiver Supported Exercise (FITWISE) for pre-frail and frail community-dwelling older adults aged 60 years and older. Frailty is associated with reduced physical function, increased risk of falls, and higher healthcare utilization among older adults. Home-based interventions supported by informal caregivers and facilitated by digital technology may help improve exercise participation and health outcomes in this population. The main questions this study aims to answer are: 1. Whether the FITWISE intervention is feasible in terms of recruitment, participant engagement, adherence, retention, and safety. 2. Whether the FITWISE intervention improves physical performance and other health-related outcomes among pre-frail and frail community-dwelling older adults. Researchers will compare two intervention groups with a control group to determine whether the FITWISE intervention improves health outcomes. Participants will be randomly assigned to one of three groups: * Intervention Group A: Caregiver-mediated multi-component exercise supported by an exergaming system. * Intervention Group B: The same exercise program with additional caregiver-delivered psychosocial support. * Control Group: General health education and usual activities without the FITWISE intervention. The intervention will last 24 weeks and will include an active 12-week intervention phase followed by a 12-week maintenance phase. Outcome measures such as physical performance, frailty status, cognitive function, social support, quality of life, and selected health indicators will be assessed at baseline and after the intervention.

In Singapore, 64.4% of school-age children sleep less than the minimum recommended duration of 9 hours on school nights, thus risking poor mental, cognitive, and brain health. These short-sleeping children, however, spend on average 2.5 hours per school day on non-academic media use, revealing the potential of reducing their screen time for more sleep. Previous interventions targeted at reducing media use and/or improving sleep among school-age children, though effective in increasing sleep, required cooperation from schools, extensive personnel training, and high commitment of participants, rendering them difficult to implement in Singapore. Existing interventions also focused on evening or pre-bedtime screen use, and took a one-size-fits-all approach, ignoring individual differences in the duration, type, and purpose of media use throughout the day. Here, we propose a scalable approach to curtail media use based on individual need throughout the day. We will conduct a randomised controlled trial during term time, recruiting 150 children, aged 6-12 years, who on school days, sleep less than 8 hours and spend more than 2 hours on media use. At baseline, all participants will record their time use patterns. The research staff will then help the intervention group to repurpose at least 60 minutes of media use per school day for sleep. Importantly, participants can decide the type, timing and duration of media use to curtail, thus giving them a sense of agency and mastery, while boosting their self-efficacy, a vital ingredient in behavioural change. The intervention group will follow this personalised schedule for 2 weeks, while the control group will be in a free-living condition. Two weeks after the intervention has ended, the intervention group will undergo follow-up assessments. Throughout the study, sleep, time use, cognitive functions, and psychological well-being will be assessed daily. Other cognitive tasks and questionnaires will be conducted during 2-3 lab/school-classroom visits, with one-third of the participants also undergoing high-density electroencephalography to measure brain activity.

Diet is a key determinant of overall health, with growing evidence associating dietary patterns with allergic diseases. Among these, atopic dermatitis (AD) is of particular interest as it often represents the earliest manifestation of the atopic triad. Investigating dietary interventions in AD therefore provides a relevant model to better understand how diet may influence the onset and progression of allergic disease more broadly.

The global ageing population is increasingly affected by age-related diseases, which are challenging healthcare systems. Current treatments often extend lifespan without improving healthspan. The geroscience hypothesis suggests that targeting the ageing process could prevent or delay multiple diseases, enhancing healthspan. Fucoidan, a sulfated polysaccharide from brown macroalgae, is a safe dietary supplement with Sirtuin-6 (SIRT6) activating properties, which are linked to longevity. Clinical studies have shown that it reduces inflammatory markers associated with biological aging and frailty and influences DNA methylation in vitro and in vivo; however, its effects on human DNA methylation remain unknown.

Frailty is associated with biological changes in the gut microbiome and immune system, along with marked declines in physical and cognitive function, leading to an overall reduction in quality of life. Prefrailty represents an early stage where interventions may prevent or reverse these declines. This study aims to evaluate whether a 12-week combined Synbiotic enriched oral nutritional supplement and supervised exercise program can improve muscle strength and mass, gut microbiome composition, immune function, and cognitive performance in prefrail adults aged 50-80 years.

As the population ages, the growing prevalence of age-related diseases is creating substantial challenges for healthcare systems worldwide. Current therapeutic strategies often target individual diseases and decrease mortality without improving healthspan. The geroscience hypothesis suggests that targeting the ageing process itself could prevent, delay, or manage the severity of multiple age-related diseases concurrently, thereby improving overall healthspan and reducing healthcare burdens. Emerging research highlights several interconnected hallmarks of aging, such as mitochondrial dysfunction, chronic inflammation, impaired autophagy, and immune dysregulation, as modifiable through targeted interventions. Precision geromedicine represents a paradigm shift in addressing these processes, combining baseline diagnostics with individualized treatment strategies that adapt over time based on patient response. This approach integrates lifestyle modifications, dietary supplements, and pharmacological agents to optimize physical, cognitive, and immune function across the lifespan .

The goal of this study is to understand how light sensitivity in the eye affects sleep, mood, alertness, and cognition in adults with glaucoma compared to healthy individuals aged 45-75 years. The main questions it aims to answer are: 1. Do patients with glaucoma experience poorer sleep, mood, alertness, and cognitive function than age-matched healthy adults? 2. Are these changes related to reduced light sensitivity in special retinal cells called intrinsically photosensitive retinal ganglion cells (ipRGCs), lost in glaucoma? 3. Can exposure to safe, full-spectrum indoor light help improve these functions? Researchers will compare patients with glaucoma and age-matched healthy controls to see if differences in light sensitivity can explain changes in non-visual light responses (i.e., sleep, mood, alertness, and cognition) and whether full-spectrum light exposure can enhance alertness and wellbeing. Participants will: 1. Complete eye exams and baseline questionnaires about their sleep, daytime sleepiness, mood, and wellbeing. 2. Wear a wrist-worn device for 8-16 days to record their sleep patterns and light exposure. 3. Visit the laboratory for cognitive and attention tests following exposure to two lighting conditions (randomized, cross-over): * Standard indoor light (\~300 lux) * Full-spectrum light (\~1000 lux) This study will help researchers understand how glaucoma affects the brain beyond vision and explore whether light-based interventions can improve quality of life for people living with glaucoma.

One important mechanism of action of GLP1 RA is the improvement in endothelial function, which may be evaluated by the assessment of cerebral vasodilatory reserve (CVR) in patients with severe ICAD. The investigators believe that GLP1 RA would be beneficial for patients with severe ICAD and lead to an improvement in cerebral vasodilatory reserve (CVR) in patients with severe and recently symptomatic stenosis of intracranial carotid artery (ICA) or middle cerebral artery (MCA). In this open label randomised clinical trial, patients with recently symptomatic and severe stenosis of intracranial carotid artery (ICA) or middle cerebral artery (MCA) with impaired cerebral vasodilatory reserve (CVR) will be included. CVR will be measured with transcranial Doppler (TCD) breath holding index and acetazolamide-challenged single photon emission computed tomography (SPECT). Patients meeting the eligibility criteria would be randomised to receive best medical therapy (according to the international guidelines and institutional practices) or Dulaglutide subcutaneous injection (0.75mg and titrating to 1.5mg, if indicated) once a week, in addition to the best medical therapy. CVR will be measured again at the completion of 1 year. MRI of the brain will be repeated to evaluate any new ischaemic brain lesions. All patients would be followed up for two years for cerebral ischaemic events. The investigators hypothesize that addition of GLP1 RA therapy would lead to a reduction of at least 4 units in CVR on SPECT as compared to best medical therapy.

The goal of this clinical trial is to evaluate whether the optimization of daily exposure to light in primary school children can lead to better myopia prevention and control. The trial also aims to better understand the impact of light exposure on sleep and cognitive performance in children. This trial has 3 arms namely, (1) a technical intervention arm, (2) a digital intervention arm, and (3) a control arm. 1. technical intervention - which involves changing of classroom lighting in primary schools to ceiling lights that mimic the spectral composition of sunlight and fluctuates in intensity. Parents of children within that arm will have a sham smart-phone application (s-LightUP) 2. digital intervention - which involves standard classroom lighting and giving parents an interventional smart-phone application (i-LightUP) that will be coupled with their child's light and activity sensor (wrist worn device ). The interventional app will provide individually tailored recommendation based on their children's behaviour (data feedback that is collected from the light and activity monitoring watch). The interventional app would then send reminder prompts/notifications to encourage parents help their children achieve required amounts of myopia-preventive light quantum target set per day. 3. Standard care or control group which involves standard classroom lighting and parents having a sham smart-phone application (s-LightUP) Participants will: * be randomised to receive either no intervention (control group), technical intervention (light intervention that mimics sunlight) or digital intervention (parents having an app that syncs with child's light and activity sensor which will provide feedback to parents to encourage and recommends increment of outdoor activities and hours). * have their myopia progression monitored every 6 monthly and cognitive assessment done once every 3 months over a year. * wear the light and activity sensor watches throughout the 1-year study period as much as possible (minimum 1 week per month) except for wet water activities such as swimming, diving and showering for research data collection purpose.

The goal of this two-armed, parallel-design, pre-/post-intervention assessment clinical trial is to learn if a digital and interactive website helps to improve advance care planning (ACP) engagement among caregivers of patients with serious illness. The main questions it aims to answer are: Does the website increase ACP engagement of caregivers of patients with serious illness? Researchers will compare the digital and interactive website to the usual care (a digital booklet) to see if the digital intervention works to improve ACP engagement among caregivers. Participants who are caregivers will: * Be introduced to a digital website and asked to explore the site over the course of the study. * Complete four self-administered questionnaires (baseline, one-week, six-week, and six-month). Participants who are patients will not have any intervention assigned and will only have their observational data collected through four interviewer-administered questionnaires (baseline, one-week, six-week, and six-month)

The goal of this clinical trial is to learn if a digital health literacy program using mobile phone chat-based application called WISDOM (WhatsApp Intervention for Seniors' Digital and cOgnitive Management) can help older adults in Singapore with fewer resources improve their digital health skills and support brain health. The main questions it aims to answer are: * Is it feasible to run WISDOM in senior centres, and will participants join and stay in the program? * Does WISDOM help older adults find and use online health information? * Does WISDOM help older adults make health decisions and impact brain functions? * What do participants think about WISDOM, and how can it be improved? Researchers will compare two groups: * WISDOM group: Participants will join a 6-week program with face-to-face learning sessions and WhatsApp activities about digital health skills. Extra support will be given if needed. * Control group: Participants will continue with their usual activities at the senior centres. Participants in the WISDOM group will: * Join weekly face-to-face sessions for 6 weeks * Use WhatsApp to complete learning activities

This study addresses the growing burden of stroke in Singapore and highlights the lack of rehabilitation services for return to work after stroke. Despite functional physical recovery, many stroke survivors experience persistent impairments that hinder return-to-work. To bridge this gap, the study will implement a community-based brain health programme targeting cognitive and vocational outcomes in stroke survivors. Caregivers will also be included due to their critical support role. The study will assess the intervention's feasibility, acceptability, and its impact on cognitive function, return-to-work, neuroplasticity, psychosocial health, fatigue, and self-care.

The goal of this interventional study is to examine the dose-response effect of Community Dance Programme (CDP) on the physical, cognitive and psychological health of pre-frail and mildly frail community-dwelling older adults. The main questions it aims to answer are: Hypothesis 1: Two sessions of CDP per week (75 minutes each) significantly increase the physical outcomes (i.e. CFS, EFS, SPPB, grip strength) of community-dwelling older adults as compared to one session of CDP per week. Hypothesis 2: Two sessions of CDP per week significantly improve the cognitive outcomes (i.e. MoCA, SDMT) of community-dwelling older adults as compared to one session of CDP per week. Hypothesis 3: Two sessions of CDP per week significantly improve the psychosocial outcomes (i.e. WHOQOL-OLD, De Jong Giervald Loneliness Scale, GPIC scale, SHS, SSQ) of community-dwelling older adults as compared to one session of CDP per week. Intervention: The participants will be asked to attend two sessions of CDP per week for 12 weeks at their respective Active Ageing Centres (AACs). Active control: The participants will be asked to attend one session of CDP per week for 12 weeks AACs. * The participants will be asked to go to the AACs at baseline and after 12 weeks of CDP intervention for the collection of data. * The participants will be asked to wear fitness trackers to track their heart rates during the CDP sessions to ensure that the dance curriculum is kept within the moderate intensity.

The Care4Senior mobile Application, Intensive Aerobic Resistance Training and Brain Health (CIRTAB) trial aim to test the effectiveness of an exercise, cognitive and lifestyle intervention amongst older adults over a 12-weeks trial period to prevent frailty and promote social bonding.

Anxiety and depression are highly prevalent mental health disorders that impose a significant burden on individuals and public health systems worldwide (GBD 2019 Mental Disorders Collaborators, 2022). Although many existing treatments focus on symptom reduction through targeting negative emotions, fewer interventions specifically enhance positive emotional experiences, despite growing evidence that low positive affect is a key feature of both anxiety and depression. Face-to-face psychologist-led positive affect therapy (PAT) is a promising intervention that aims to cultivate positive emotions, engagement, and meaning, potentially leading to greater improvements in emotional well-being than traditional approaches (Craske et al., 2019). However, empirical evaluations of digitally-delivered, asynchronously-coached, scalable versions of the PAT remain limited (Craske et al., 2024; Firth et al., 2017). The present study thus aims to investigate the comparative efficacy of a digital positive affect intervention (PAI) in reducing symptoms of anxiety and depression and enhancing overall mental health outcomes. We utilize a two-arm randomized controlled trial (RCT) design to investigate the effectiveness of a six-week digitally delivered positive affect intervention (vs. self-monitoring active control; Zainal \& Newman, 2023) in reducing self-reported symptoms of anxiety and depression, as well as other secondary psychosocial outcomes, including sleep quality, quality of life, and emotion regulation. The treatment program comprises weekly evidence-based therapeutic material delivered online, and daily mental health (MH) mobile application prompts delivered thrice a day for the 6-week treatment period, based on evidence-based positive affect therapy principles. The active comparator comprises self-monitoring MH mobile application prompts for the 6-week treatment period. All participants will be assessed on several psychosocial outcomes at mid-treatment, post-treatment, and at 3-, 6-, and 12-month follow-up. The study hypothesizes that participants randomized to the digital PAI will experience greater improvement in anxious and depressive symptoms both immediately after treatment and up to a year later, compared to the self-monitoring MH app. Findings will contribute to growing evidence that digital PAI is an efficacious and feasible treatment to target and enhance positive emotions and related mental health outcomes in adults experiencing anxiety and depression.

TREAT-GNB is an innovative trial to expedite the evaluation of various antibiotic choices and treatment strategies for severe multidrug-resistant Gram-negative bacterial infections, specifically bloodstream and lower respiratory tract infections. This approach combines platform trial elements with adaptive clinical designs to streamline the evaluation of various treatment options and optimise resource utilisation. The overall aim of the TREAT-GNB platform trial is to identify interventions that improve survival in patients with severe infections due to Gram-negative bacteria. In the CR-GNB silo of TREAT-GNB, the primary objective is to quantify the effect on all-cause mortality at 28 days of a range of interventions in patients with bloodstream infections, ventilator-associated pneumonia, and hospital-acquired pneumonia caused by CR-GNB.

This cross-sectional study aims to investigate the associations between dietary intake, cardiometabolic health markers, and gut microbiota composition in Singapore adults.