Restoring Bile Acid Homeostasis Via Lifestyle Adjustments to Prevent the Development of Liver Cancer

NCT07111130 | Not Yet Recruiting

• 1 other identifier: AHCC14
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 14

Brief 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).

Conditions

Liver Diseases

Keywords

Hepatocellular Carcinoma (HCC); Non-viral HCC; Interventional Study; Lifestyle Adjustments; Bile Acid, Microbiome and Liver Health Modulation

Outcome Measures

Primary Outcomes (7)

• Hepatocarcinogenic risk change in relation to metabolomics profile.

  Change in the bile acid profile pre- and post-intervention.

  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.

  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.

  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.

  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.

  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.

  Up to 12 months.

• Long-term HCC incidence against a matched control within the ELEGANCE cohort.

  Up to 12 months.

Study Arms (1)

12-week Intervention

EXPERIMENTAL

12-week lifestyle intervention.

Other: 12-week Lifestyle Intervention

Interventions

12-week Lifestyle Intervention OTHER

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.

12-week Intervention

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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.
• Negative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody
• High-risk bile acid profile, defined as a 12-non-hydroxy/12-hydroxy bile acid ratio below the threshold determined from ELEGANCE cohort data.
• Patient is able to comply with scheduled visits, assessments and other study procedures.
• Patient is willing to provide informed consent before enrolment in the study.

You may not qualify if:

• The following criteria should be checked at the time of enrolment. If ANY applies, the patient must not be included in the study:
• 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.
• Patient with Child Pugh C or decompensated cirrhosis at time of enrolment (based on the judgement of the Investigator).
• Patient with active hepatic encephalopathy at time of enrolment.
• Patient is known to be positive for the Human Immunodeficiency Virus (HIV).
• Patient has chronic liver diseases apart from steatosis or compensated cirrhosis (e.g., autoimmune hepatitis, primary biliary cholangitis. etc.).
• Uncontrolled diabetes mellitus requiring special dietary management or persistent unacceptable HbA1c levels.
• Use of weight-loss medications (e.g., GLP-1 agonists, Orlistat) within three months prior to enrolment or planned use during the study period.
• History of bariatric surgery or planned bariatric surgery during the study period.
• Patient has significant comorbidities expected to limit life expectancy to less than one year, or that would render diet or exercise unsafe
• Diseases involving muscles, bones or joints that may impact the subjects' performance during exercise testing and exercise rehabilitation
• Co-morbidities that may adversely affect exercise performance
• Requiring an assistive aid with walking
• Conditions that require strict dietary restrictions or impair ability to follow dietary interventions
• Patient has significant gastrointestinal diseases affecting nutrient absorption or requiring a special diet incompatible with study diet.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Perspectum: collaborator
• BUZUD Pte Ltd: collaborator
• Asian Microbiome Library (AMiLi) Pte Ltd: collaborator

Study Sites (14)

National University Hospital

Singapore, 119074, Singapore

Location

SingHealth Polyclinics - Bukit Merah

Singapore, 150163, Singapore

Location

National Cancer Center Singapore

Singapore, 168583, Singapore

Location

SingHealth Polyclinics - Outram

Singapore, 168937, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

SingHealth Polyclinics - Marine Parade

Singapore, 440080, Singapore

Location

SingHealth Polyclinics - Bedok

Singapore, 469662, Singapore

Location

SingHealth Polyclinics - Pasir Ris

Singapore, 519466, Singapore

Location

SingHealth Polyclinics - Tampines

Singapore, 529203, Singapore

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Sengkang General Hospital

Singapore, 544886, Singapore

Location

SingHealth Polyclinics - Sengkang

Singapore, 545025, Singapore

Location

SingHealth Polyclinics - Punggol

Singapore, 820681, Singapore

Location

MeSH Terms

Conditions

Liver Diseases; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Study Officials

• Professor Pierce Chow, MD, PhD

  National Cancer Centre, Singapore

  STUDY CHAIR

Central Study Contacts

Professor Pierce Chow, MD, PhD

CONTACT

+65 6306 5424; pierce.chow.k.h@singhealth.com.sg

Dr Yuxin GUO, MD

CONTACT

guo.yuxin@singhealth.com.sg

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 15, 2025
• First Posted: August 8, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (14)