12-week Lifestyle Intervention: 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.
Study summary
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).
Eligibility
Sex
ALL
Min age
40 Years
Max age
90 Years
Healthy volunteers
No
Inclusion Criteria:
The following criteria are to be checked at the time of enrolment. The patient may only be included in the study if ALL of the following statements are FULFILLED:
1. The patient is an existing participant of the ELEGANCE study and shows no evidence of hepatocellular carcinoma (HCC) at the time of enrolment into RE-BALANCE.
2. Male and female patients aged 50 to 90 years at the time of informed consent are eligible. However, patients with cirrhosis may be included if they are aged 40 to 90 years.
3. Negative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody
4. High-risk bile acid profile, defined as a 12-non-hydroxy/12-hydroxy bile acid ratio below the threshold determined from ELEGANCE cohort data.
5. Patient is able to comply with scheduled visits, assessments and other study procedures.
6. Patient is willing to provide informed consent before enrolment in the study.
Exclusion Criteria:
The following criteria should be checked at the time of enrolment. If ANY applies, the patient must not be included in the study:
1. Patient with confirmed diagnosis of HCC by the American Association for the Study of the Liver Disease (AASLD) imaging criteria or histology / cytology within the last 5 years.
2. Patient with Child Pugh C or decompensated cirrhosis at time of enrolment (based on the judgement of the Investigator).
3. Patient with active hepatic encephalopathy at time of enrolment.
4. Patient is known to be positive for the Human Immunodeficiency Virus (HIV).
5. Patient has chronic liver diseases apart from steatosis or compensated cirrhosis (e.g., autoimmune hepatitis, primary biliary cholangitis. etc.).
6. Uncontrolled diabetes mellitus requiring special dietary management or persistent unacceptable HbA1c levels.
7. Use of weight-loss medications (e.g., GLP-1 agonists, Orlistat) within three months prior to enrolment or planned use during the study period.
8. History of bariatric surgery or planned bariatric surgery during the study period.
9. Patient has significant comorbidities expected to limit life expectancy to less than one year, or that would render diet or exercise unsafe
1. Diseases involving muscles, bones or joints that may impact the subjects' performance during exercise testing and exercise rehabilitation
2. Co-morbidities that may adversely affect exercise performance
3. Requiring an assistive aid with walking
4. Conditions that require strict dietary restrictions or impair ability to follow dietary interventions
10. Patient has significant gastrointestinal diseases affecting nutrient absorption or requiring a special diet incompatible with study diet.
11. Pregnancy or breastfeeding
12. Current use of medications or supplements that significantly alter bile acid gastrointestinal absorption (e.g., bile acid sequestrants) that cannot be safely discontinued.
13. Patient has severe food allergies or intolerances incompatible with the provided study diet.
14. Patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
15. Patient is unable to provide informed consent or refuse blood taking and other investigations including LMS scans.
16. Patient has any other condition which, in the opinion of the Investigators, would make the patient unsuitable for enrolment or could interfere with completion of the study.
Primary outcome measure(s)
Hepatocarcinogenic risk change in relation to metabolomics profile. — Pre-intervention (Baseline), Post-intervention (3-month) Change in the bile acid profile pre- and post-intervention.
Hepatocarcinogenic risk change in relation to metagenomics profile. — Pre-intervention (Baseline), Post-intervention (3-month) Change in the gut microbiome alpha and beta diversity pre- and post-intervention.
Hepatocarcinogenic risk change in relation to liver health profile. — Pre-intervention (Baseline), Post-intervention (3-month) Change in the hepatic steatosis and fibrosis as measured by LMS-CT1 MRI pre- and post-intervention.
Sustained change in hepatocarcinogenic risk in relation to metabolomics profile. — Up to 12 months. Sustained change in the bile acid profile post-intervention.
Sustained change in hepatocarcinogenic risk in relation to metagenomics profile. — Up to 12 months. Sustained change in the gut microbiome alpha and beta diversity post-intervention.
Sustained change in hepatocarcinogenic risk in relation to liver health profile. — Up to 12 months. Sustained change in the hepatic steatosis and fibrosis as measured by LMS-CT1 MRI post-intervention.
Long-term HCC incidence against a matched control within the ELEGANCE cohort. — Up to 12 months.
Trial sites (14)
Facility
City
Region
Status
National University Hospital
Singapore
Singapore
SingHealth Polyclinics - Bukit Merah
Singapore
Singapore
National Cancer Center Singapore
Singapore
Singapore
SingHealth Polyclinics - Outram
Singapore
Singapore
Singapore General Hospital
Singapore
Singapore
Tan Tock Seng Hospital
Singapore
Singapore
SingHealth Polyclinics - Marine Parade
Singapore
Singapore
SingHealth Polyclinics - Bedok
Singapore
Singapore
SingHealth Polyclinics - Pasir Ris
Singapore
Singapore
SingHealth Polyclinics - Tampines
Singapore
Singapore
Changi General Hospital
Singapore
Singapore
Sengkang General Hospital
Singapore
Singapore
SingHealth Polyclinics - Sengkang
Singapore
Singapore
SingHealth Polyclinics - Punggol
Singapore
Singapore
More National Cancer Centre, Singapore trials in Singapore
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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