Liver DiseasesRE-BALANCENCT07111130
Restoring Bile Acid Homeostasis Via Lifestyle Adjustments to Prevent the Development of Liver Cancer
A study testing 12-week Lifestyle Intervention in people with Liver Diseases, run by National Cancer Centre, Singapore at 14 sites in Singapore.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 90 years
- Conditions the study is for
- Liver Diseases
- What is being tested?
- 12-week Lifestyle Intervention
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 14 sitesSingapore
- Study dates
- Jul 2026to Mar 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.).
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- 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.
- Pregnancy or breastfeeding
- Current use of medications or supplements that significantly alter bile acid gastrointestinal absorption (e.g., bile acid sequestrants) that cannot be safely discontinued.
- Patient has severe food allergies or intolerances incompatible with the provided study diet.
- Patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
- Patient is unable to provide informed consent or refuse blood taking and other investigations including LMS scans.
- 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.
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Dr Yuxin GUO, MD contact
14 sites in 1 country
Singapore14 sites
National University Hospital
Singapore, 119074
SingHealth Polyclinics - Bukit Merah
Singapore, 150163
National Cancer Center Singapore
Singapore, 168583
Professor Pierce CHOW, MD, PhD
SingHealth Polyclinics - Outram
Singapore, 168937
Singapore General Hospital
Singapore, 169608
Tan Tock Seng Hospital
Singapore, 308433
SingHealth Polyclinics - Marine Parade
Singapore, 440080
SingHealth Polyclinics - Bedok
Singapore, 469662
SingHealth Polyclinics - Pasir Ris
Singapore, 519466
SingHealth Polyclinics - Tampines
Singapore, 529203
Changi General Hospital
Singapore, 529889
Sengkang General Hospital
Singapore, 544886
SingHealth Polyclinics - Sengkang
Singapore, 545025
SingHealth Polyclinics - Punggol
Singapore, 820681
About this study
Official title: Prospective Interventional Study Evaluating the Modulation of Bile Acid Profiles, Gut Microbiome and Liver Health Through Lifestyle Adjustments in Individuals at High Risk of Developing Liver Cancer.
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).
Read the detailed description
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.
- Conditions
- Liver Diseases
- Being tested
- 12-week Lifestyle Intervention
- Keywords
- Hepatocellular Carcinoma (HCC), Non-viral HCC, Interventional Study, Lifestyle Adjustments, Bile Acid, Microbiome and Liver Health Modulation
- Medical subject headings
- Liver Diseases, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
12-week Lifestyle InterventionOther
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 group | Role | What they receive |
|---|---|---|
| 12-week Intervention | Experimental | 12-week lifestyle intervention. Receives: Other: 12-week Lifestyle Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatocarcinogenic risk change in relation to metabolomics profile.
Change in the bile acid profile pre- and post-intervention.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 12 months.
Long-term HCC incidence against a matched control within the ELEGANCE cohort.
Measured: Up to 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2025
- Study startJul 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Perspectum, BUZUD Pte Ltd, Asian Microbiome Library (AMiLi) Pte Ltd
- Responsible party
- Sponsor
- Investigators
- Professor Pierce Chow, MD, PhD, Study chair, National Cancer Centre, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07111130
- Sponsor's protocol ID
- AHCC14
- Acronym
- RE-BALANCE
- Status last verified
- May 2026
- First submitted
- 15 Jul 2025
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Interventional Study Evaluating the Modulation of Bile Acid Profiles, Gut Microbiome and Liver Health Through Lifestyle Adjustments in Individuals at High Risk of Developing Liver Cancer.
- ClinicalTrials.gov ID
- NCT07111130
- Acronym / sponsor ID
- RE-BALANCE / AHCC14
- Conditions
- Liver Diseases
- Keywords
- Hepatocellular Carcinoma (HCC), Non-viral HCC, Interventional Study, Lifestyle Adjustments, Bile Acid, Microbiome and Liver Health Modulation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Collaborators
- Perspectum, BUZUD Pte Ltd, Asian Microbiome Library (AMiLi) Pte Ltd
- Study start
- Jul 2026 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2028 (estimated)
- First posted
- 8 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| 12-week Intervention | Experimental | Other: 12-week Lifestyle Intervention12-week lifestyle intervention. |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 12-week Lifestyle InterventionEligible 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. | Other | 12-week Intervention |
Primary outcome
Hepatocarcinogenic risk change in relation to metabolomics profile.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months.
Sustained change in the bile acid profile post-intervention.
Sustained change in hepatocarcinogenic risk in relation to metagenomics profile.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr Yuxin GUO, MD contact
Professor Pierce Chow, MD, PhD study chair
National Cancer Centre, Singapore
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 12-week Lifestyle Intervention in people with Liver Diseases, run by National Cancer Centre, Singapore at 14 sites in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Professor Pierce Chow, MD, PhD (+65 6306 5424, pierce.chow.k.h@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatocarcinogenic risk change in relation to metabolomics profile. (time frame: Pre-intervention (Baseline), Post-intervention (3-month)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.