This is a prospective, single-arm, non-randomized interventional study nested within the existing ELEGANCE cohort. Patients eligible for the RE-BALANCE study will be selected from the ELEGANCE cohort based on predefined high-risk criteria, specifically a low 12-non-hydroxy/12-hydroxy bile acid ratio indicative of elevated hepatocarcinogenic risk. The study comprises Baseline Assessments (Visit 1), Intervention Visits (Visit 2-8), and Follow-up Assessments (Visit 9-11).
Participants will undergo a structured 12-week lifestyle intervention comprising a low-carbohydrate, high-fibre dietary plan and a prescribed physical activity program targeting at least 150 minutes of moderate-intensity exercise per week. Standardized meal provision and wearable fitness tracking devices will be used to support adherence throughout the intervention period. Biological assessments will be conducted at baseline (Visit 1), mid-intervention (Visit 6), and end-of-intervention (Visit 9), including blood sampling for bile acid profiling and stool sampling for gut microbiome sequencing. Liver health evaluation will be conducted at baseline (Visit 1) and end-of-intervention (Visit 9) to assess patient's change in liver health. Extended biological assessments (Visit 10-11) and liver health evaluation through LMS-CT1 imaging (Visit 11) will be performed post-intervention to evaluate the sustainability of the observed changes. Participants will continue to receive standard-of-care surveillance in parallel during the study. In the event of clinical suspicion for hepatocellular carcinoma during surveillance imaging, participants will undergo confirmatory diagnostic imaging and, if diagnosed, will be referred for standard clinical management. Participants diagnosed with HCC during the study will be withdrawn from the active intervention phase. Their data up to the point of diagnosis will be included in analysis, and they will revert to standard-of-care HCC management. Ongoing follow-up for clinical outcomes may continue under the parent ELEGANCE study framework. The study will enrol approximately 90 high-risk NBNC patients identified from the ELEGANCE cohort. Accrual is expected to be completed within 6 to 9 months. The active intervention will last 12 weeks, with subsequent observational follow-up extending up to 12 months post-intervention to assess the durability of metabolic, microbiome, and imaging changes and monitor the incidence of hepatocellular carcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Eligible participants within the existing ELEGANCE cohort will undergo a structured 12-week lifestyle intervention comprising a low-carbohydrate, high-fibre dietary plan and a prescribed physical activity program targeting at least 150 minutes of moderate-intensity exercise per week. Standardized meal provision and wearable fitness tracking devices will be used to support adherence throughout the intervention period.
National University Hospital
Singapore, Singapore
SingHealth Polyclinics - Bukit Merah
Singapore, Singapore
National Cancer Center Singapore
Singapore, Singapore
Hepatocarcinogenic risk change in relation to metabolomics profile.
Change in the bile acid profile pre- and post-intervention.
Time frame: Pre-intervention (Baseline), Post-intervention (3-month)
Hepatocarcinogenic risk change in relation to metagenomics profile.
Change in the gut microbiome alpha and beta diversity pre- and post-intervention.
Time frame: Pre-intervention (Baseline), Post-intervention (3-month)
Hepatocarcinogenic risk change in relation to liver health profile.
Change in the hepatic steatosis and fibrosis as measured by LMS-CT1 MRI pre- and post-intervention.
Time frame: Pre-intervention (Baseline), Post-intervention (3-month)
Sustained change in hepatocarcinogenic risk in relation to metabolomics profile.
Sustained change in the bile acid profile post-intervention.
Time frame: Up to 12 months.
Sustained change in hepatocarcinogenic risk in relation to metagenomics profile.
Sustained change in the gut microbiome alpha and beta diversity post-intervention.
Time frame: Up to 12 months.
Sustained change in hepatocarcinogenic risk in relation to liver health profile.
Sustained change in the hepatic steatosis and fibrosis as measured by LMS-CT1 MRI post-intervention.
Time frame: Up to 12 months.
Long-term HCC incidence against a matched control within the ELEGANCE cohort.
Time frame: Up to 12 months.
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Purpose
PREVENTION
Masking
NONE
Enrollment
90
SingHealth Polyclinics - Outram
Singapore, Singapore
Singapore General Hospital
Singapore, Singapore
Tan Tock Seng Hospital
Singapore, Singapore
SingHealth Polyclinics - Marine Parade
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SingHealth Polyclinics - Bedok
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SingHealth Polyclinics - Pasir Ris
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SingHealth Polyclinics - Tampines
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...and 4 more locations