Liver FibrosisSURGIC-LiverNCT07102979
Remedial Mechanism of Simvastatin and Ursodeoxycholic Acid in Liver Cirrhosis: Crosstalk of Bile Secretion, Gut Microbiome, and Host Immune Response
A study testing Ursodeoxycholic Acid (URSO) and Simvastatin in people with Liver Fibrosis, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
This exploratory, randomized, open-label pilot study evaluated gut microbiota, fecal bile acid profiles, inflammatory markers, and fibrosis-related biomarkers in adults with chronic hepatitis B or hepatitis C after viral control. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Fibrosis
- What is being tested?
- Ursodeoxycholic Acid (URSO) and Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Jan 2024to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 to 75 years
- Diagnosed with advanced fibrosis; the cohort was operationally defined by a FibroScan liver stiffness measurement of ≥9.5 kPa.
- Achieved sustained virological response (SVR) at least 6 months after hepatitis C treatment, or
- Non-replicating hepatitis B infection (undetectable viral load) for at least 6 months
- Able and willing to provide informed consent
Who cannot join
- Current or prior use of statins
- Liver decompensation (jaundice, ascites, hepatic coma, or esophagogastric varices)
- Diagnosed hepatocellular carcinoma or other liver cancers
- Alcoholic liver disease or moderate-to-severe fatty liver
- Diagnosed diabetes mellitus
- Chronic kidney disease
Show all 10Show fewer
- Use of antibiotics within the past 3 months
- Use of gastric ulcer medications such as proton pump inhibitors (PPIs)
- Pregnancy or breastfeeding
- Any condition deemed by the investigator to interfere with study participation or outcomes
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, Others, 833
About this study
Official title: Remedial Mechanisms of Simvastatin and Ursodeoxycholic Acid in Liver Cirrhosis: Crosstalk Between Bile Secretion, Gut Microbiome, and Host Immune Response
This exploratory, randomized, open-label pilot study evaluated gut microbiota, fecal bile acid profiles, inflammatory markers, and fibrosis-related biomarkers in adults with chronic hepatitis B or hepatitis C after viral control. The study included a randomized cohort with advanced liver fibrosis and a non-randomized comparison cohort without advanced fibrosis. Viral control was defined as hepatitis B virus suppression during antiviral therapy or sustained virologic response after hepatitis C treatment.
The main questions addressed by the study were:
Read more
Do participants with advanced liver fibrosis differ from those without advanced fibrosis in their baseline gut microbiota, fecal bile acid profiles, inflammatory markers, or fibrosis-related biomarkers? What within-participant changes in these measures are observed after six months of treatment with ursodeoxycholic acid (UDCA), simvastatin, or combined UDCA plus simvastatin? What descriptive patterns of change are observed across the three active-treatment groups?
Advanced liver fibrosis was operationally defined during enrollment as a FibroScan liver stiffness measurement of ≥9.5 kPa. Thirteen participants with presumed advanced liver fibrosis were randomized to observation without study medication, UDCA alone, simvastatin alone, or combined simvastatin plus UDCA. One randomized participant was subsequently excluded from the analysis after eligibility review because the advanced-fibrosis criteria were not confirmed, leaving 12 eligible randomized participants, with three participants in each study group. An additional six participants with non-advanced fibrosis, defined by a FibroScan liver stiffness measurement of <6.0 kPa, were enrolled as a non-randomized baseline comparison group.
Baseline blood and stool samples were collected from all 19 enrolled participants. The final baseline analysis set included 18 eligible participants: 12 participants with advanced fibrosis and six participants without advanced fibrosis. Follow-up blood and stool samples were collected after six months from the nine participants in the three active-treatment groups. The observation group and the non-advanced fibrosis comparison group contributed baseline data only and did not undergo post-treatment sampling.
Recruitment was substantially slower than anticipated and was discontinued after the available study funding was exhausted. The study was therefore terminated before reaching its originally planned enrollment target. The final actual enrollment was 19 participants, of whom 18 were included in the final analysis set. Because only three participants were available in each randomized study group, all treatment-related analyses were considered exploratory and hypothesis-generating. The study was not designed or adequately powered to establish clinical efficacy, histological fibrosis regression, or superiority of combination therapy.
Read the detailed description
BACKGROUND AND PURPOSE
Patients with advanced liver fibrosis remain at risk of liver-related complications even after successful control of chronic hepatitis B or hepatitis C. Alterations in the gut microbiota and bile acid metabolism may contribute to persistent inflammation and fibrosis progression through the gut-liver axis.
Ursodeoxycholic acid (UDCA) modifies the bile acid pool and may influence bile acid metabolism and signaling. Simvastatin may have anti-inflammatory, endothelial, and antifibrotic effects. This exploratory pilot study evaluated gut microbiota, fecal bile acid profiles, inflammatory markers, and fibrosis-related biomarkers in adults with chronic viral hepatitis after viral control.
The study had two main objectives: first, to compare baseline biological characteristics between participants with and without advanced liver fibrosis; and second, to explore within-participant changes after six months of treatment with UDCA, simvastatin, or their combination.
STUDY DESIGN
This was a prospective, single-center, randomized, open-label exploratory pilot study.
Participants with presumed advanced liver fibrosis were assigned by block randomization, with a planned 1:1:1:1 allocation, to one of four groups:
Observation without study medication; UDCA 10 mg/kg/day for six months; Simvastatin 40 mg/day for six months; or Simvastatin 40 mg/day plus UDCA 10 mg/kg/day for six months.
A separate non-randomized cohort of participants without advanced fibrosis was enrolled for baseline comparison.
Eligible participants had chronic hepatitis B with viral suppression during antiviral therapy or chronic hepatitis C with sustained virologic response after antiviral treatment. During study enrollment, advanced liver fibrosis was operationally defined as a FibroScan liver stiffness measurement of at least 9.5 kPa. The non-advanced fibrosis comparison cohort was defined by a liver stiffness measurement of less than 6.0 kPa.
ACTUAL ENROLLMENT AND FOLLOW-UP
The study was originally planned to enroll 120 participants in the four randomized groups and an additional 30 participants in the non-randomized comparison cohort.
Recruitment began in January 2024. The study and recruitment period was subsequently extended through December 2025 with formal Institutional Review Board approval. Despite the approved extension, recruitment remained substantially slower than anticipated, and the available study funding was exhausted before the planned sample size could be reached. Recruitment was therefore discontinued, and the study was terminated early.
The final actual enrollment was 19 participants. Thirteen participants with presumed advanced fibrosis were randomized. One participant assigned to the UDCA group was subsequently excluded from the final analyses because the advanced-fibrosis eligibility criteria were not confirmed during post-randomization review. This participant remained included in the actual enrollment count.
The final analysis set therefore included 18 eligible participants: 12 participants with advanced fibrosis, with three participants in each randomized group, and six participants with non-advanced fibrosis in the non-randomized comparison cohort.
Baseline blood and stool samples were collected from all enrolled participants. Samples from the participant whose eligibility was not confirmed were excluded from the final analyses. Six-month follow-up samples were collected from the nine participants in the three active-treatment groups. The observation group and the non-advanced fibrosis comparison group contributed baseline data only.
STUDY ASSESSMENTS
Study assessments included clinical characteristics, stool microbiota profiles, targeted fecal bile acid measurements, inflammatory markers, and fibrosis-related biomarkers.
Microbiota assessments included measures of microbial diversity and taxonomic composition. Fecal bile acid assessments included selected primary, secondary, and conjugated bile acids. Changes from baseline to six months were evaluated in participants receiving active treatment.
Because of the small number of participants and the absence of longitudinal sampling in the observation and non-advanced fibrosis comparison groups, all treatment-related assessments were considered exploratory and hypothesis-generating. The study was not adequately powered to establish clinical efficacy, histological fibrosis regression, or superiority of one treatment regimen over another.
PROTOCOL NONCOMPLIANCE AND REGULATORY HANDLING
The operational liver-stiffness criterion applied during enrollment differed from the more restrictive fibrosis-related eligibility criteria specified in the original protocol and initial ClinicalTrials.gov record. Consequently, some participants included in the operationally defined advanced-fibrosis cohort did not meet the original fibrosis-related eligibility definition.
This protocol noncompliance was formally reported to the Institutional Review Board and was acknowledged on June 8, 2026 (IRB protocol no. 202201398A3; noncompliance report no. 202201398A3C2001). The Institutional Review Board subsequently accepted the study closure report on July 23, 2026.
The results of this prematurely terminated pilot study should therefore be interpreted as exploratory biological observations rather than confirmatory evidence of treatment efficacy.
- Conditions
- Liver Fibrosis
- Being tested
- Ursodeoxycholic Acid (URSO), Simvastatin
- Keywords
- Advanced liver fibrosis, Fecal bile salt, UDCA, Statin
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ursodeoxycholic Acid (URSO)Drug
Ursodeoxycholic acid (UDCA) was administered orally at a dose of 10 mg/kg/day for 6 months.
SimvastatinDrug
Simvastatin was administered orally at a dose of 40 mg/day for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Advanced liver fibrosis -Control Group | No intervention | Participants receive standard clinical monitoring without any investigational treatment. No simvastatin or ursodeoxycholic acid (UDCA) is administered during the 6-month study period. |
| Advanced liver fibrosis -UDCA Group | Experimental | Participants receive ursodeoxycholic acid (UDCA) at a dose of 10 mg/kg/day orally for 6 months to evaluate its effect on liver fibrosis, bile acid metabolism, and gut microbiota. Receives: Drug: Ursodeoxycholic Acid (URSO) |
| Advanced liver fibrosis -Simvastatin Group | Experimental | Participants receive simvastatin at a dose of 40 mg/day orally for 6 months. The treatment aims to assess effects on fibrosis markers, inflammation, and gut microbiota composition. Receives: Drug: Simvastatin |
| Advanced liver fibrosis -Simvastatin + UDCA Group | Experimental | Participants receive a combination of simvastatin (40 mg/day) and ursodeoxycholic acid (UDCA) (10 mg/kg/day) orally for 6 months. The combination therapy is evaluated for potential synergistic effects on fibrosis reduction, bile acid modulation, and microbiota restoration. Receives: Drug: Ursodeoxycholic Acid (URSO); Drug: Simvastatin |
| Non-advanced Fibrosis Comparison Cohort | No intervention | Participants without advanced fibrosis were enrolled as a non-randomized cohort for baseline comparison. No study medication was administered. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in liver fibrosis biomarker (TGF-β1)
Measurement of serum fibrosis-related marker TGF-β1. This will assess the antifibrotic effects of simvastatin, UDCA, and their combination in patients with stable liver cirrhosis.
Measured: Baseline and 6 months after treatment initiation
Change in liver fibrosis biomarker (Type IV collagen)
Measurement of serum fibrosis-related marker Type IV collagen. This will assess the antifibrotic effects of simvastatin, UDCA, and their combination in patients with stable liver cirrhosis.
Measured: Baseline and 6 months after treatment initiation
Secondary outcomes (2)
Change in Cirrhosis Dysbiosis Ratio (CDR)
CDR is calculated as the ratio of beneficial autochthonous bacteria (e.g., Lachnospiraceae, Ruminococcaceae, Clostridiales) to potentially pathogenic bacteria (e.g., Enterobacteriaceae, Streptococcaceae), using 16S rRNA sequencing of stool samples.
Measured: Baseline and 6 months after treatment
Change in Serum Inflammatory Cytokines
Measurement of circulating cytokines including IL-6, IL-8, IL-10 to evaluate systemic inflammatory response to intervention.
Measured: Baseline and 6 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2025
- Study start1 Jan 2024
- Primary completion22 Dec 2025
- Study completion31 Dec 2025
Why it stopped: Slow recruitment and exhaustion of available study funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Liver FibrosisStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, controlled, parallel-group study with four arms. Eligible participants with advanced liver fibrosis are randomly assigned in a 1:1:1:1 ratio to receive either (1) no treatment (control), (2) ursodeoxycholic acid (UDCA) alone, (3) simvastatin alone, or (4) a combination of simvastatin and UDCA for 6 months. Randomization is performed using block randomization to ensure balanced allocation across groups. The groups are followed in parallel, and no crossover occurs between arms. A separate healthy control group (non-cirrhotic) provides baseline microbiota and bile acid profile comparisons but is not included in the interventional randomization.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07102979
- Sponsor's protocol ID
- IRB 202201398A3
- Other IDs
- CMRPG8P0291
- Acronym
- SURGIC-Liver
- Status last verified
- Jul 2026
- First submitted
- 29 Jul 2025
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual Participant Data (IPD) will not be shared due to privacy concerns and data protection regulations. The study does not have participant consent or institutional approval for public data sharing. Aggregated results will be reported in scientific publications.
Publications
Islam KB, Fukiya S, Hagio M, Fujii N, Ishizuka S, Ooka T, Ogura Y, Hayashi T, Yokota A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81. doi: 10.1053/j.gastro.2011.07.046. Epub 2011 Aug 10.
PubMed 21839040Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011 Aug;54(2):562-72. doi: 10.1002/hep.24423. Epub 2011 Jun 26.
PubMed 21574172Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, Monteith P, Noble NA, Sikaroodi M, Gillevet PM. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012 Sep 15;303(6):G675-85. doi: 10.1152/ajpgi.00152.2012. Epub 2012 Jul 19.
PubMed 22821944Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G168-75. doi: 10.1152/ajpgi.00190.2011. Epub 2011 Sep 22.
PubMed 21940902
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Remedial Mechanisms of Simvastatin and Ursodeoxycholic Acid in Liver Cirrhosis: Crosstalk Between Bile Secretion, Gut Microbiome, and Host Immune Response
- ClinicalTrials.gov ID
- NCT07102979
- Acronym / sponsor ID
- SURGIC-Liver / IRB 202201398A3
- Conditions
- Liver Fibrosis
- Keywords
- Advanced liver fibrosis, Fecal bile salt, UDCA, Statin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment and exhaustion of available study funding.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 22 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 5 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 exploratory, randomized, open-label pilot study evaluated gut microbiota, fecal bile acid profiles, inflammatory markers, and fibrosis-related biomarkers in adults with chronic hepatitis B or hepatitis C after viral control. The study included a randomized cohort with advanced liver fibrosis and a non-randomized comparison cohort without advanced fibrosis. Viral control was defined as hepatitis B virus suppression during antiviral therapy or sustained virologic response after hepatitis C treatment.
The main questions addressed by the study were:
Do participants with advanced liver fibrosis differ from those without advanced fibrosis in their baseline gut microbiota, fecal bile acid profiles, inflammatory markers, or fibrosis-related biomarkers? What within-participant changes in these measures are observed after six months of treatment with ursodeoxycholic acid (UDCA), simvastatin, or combined UDCA plus simvastatin? What descriptive patterns of change are observed across the three active-treatment groups?
Advanced liver fibrosis was operationally defined during enrollment as a FibroScan liver stiffness measurement of ≥9.5 kPa. Thirteen participants with presumed advanced liver fibrosis were randomized to observation without study medication, UDCA alone, simvastatin alone, or combined simvastatin plus UDCA. One randomized participant was subsequently excluded from the analysis after eligibility review because the advanced-fibrosis criteria were not confirmed, leaving 12 eligible randomized participants, with three participants in each study group. An additional six participants with non-advanced fibrosis, defined by a FibroScan liver stiffness measurement of <6.0 kPa, were enrolled as a non-randomized baseline comparison group.
Baseline blood and stool samples were collected from all 19 enrolled participants. The final baseline analysis set included 18 eligible participants: 12 participants with advanced fibrosis and six participants without advanced fibrosis. Follow-up blood and stool samples were collected after six months from the nine participants in the three active-treatment groups. The observation group and the non-advanced fibrosis comparison group contributed baseline data only and did not undergo post-treatment sampling.
Recruitment was substantially slower than anticipated and was discontinued after the available study funding was exhausted. The study was therefore terminated before reaching its originally planned enrollment target. The final actual enrollment was 19 participants, of whom 18 were included in the final analysis set. Because only three participants were available in each randomized study group, all treatment-related analyses were considered exploratory and hypothesis-generating. The study was not designed or adequately powered to establish clinical efficacy, histological fibrosis regression, or superiority of combination therapy.
Detailed description
BACKGROUND AND PURPOSE
Patients with advanced liver fibrosis remain at risk of liver-related complications even after successful control of chronic hepatitis B or hepatitis C. Alterations in the gut microbiota and bile acid metabolism may contribute to persistent inflammation and fibrosis progression through the gut-liver axis.
Ursodeoxycholic acid (UDCA) modifies the bile acid pool and may influence bile acid metabolism and signaling. Simvastatin may have anti-inflammatory, endothelial, and antifibrotic effects. This exploratory pilot study evaluated gut microbiota, fecal bile acid profiles, inflammatory markers, and fibrosis-related biomarkers in adults with chronic viral hepatitis after viral control.
The study had two main objectives: first, to compare baseline biological characteristics between participants with and without advanced liver fibrosis; and second, to explore within-participant changes after six months of treatment with UDCA, simvastatin, or their combination.
STUDY DESIGN
This was a prospective, single-center, randomized, open-label exploratory pilot study.
Participants with presumed advanced liver fibrosis were assigned by block randomization, with a planned 1:1:1:1 allocation, to one of four groups:
Observation without study medication; UDCA 10 mg/kg/day for six months; Simvastatin 40 mg/day for six months; or Simvastatin 40 mg/day plus UDCA 10 mg/kg/day for six months.
A separate non-randomized cohort of participants without advanced fibrosis was enrolled for baseline comparison.
Eligible participants had chronic hepatitis B with viral suppression during antiviral therapy or chronic hepatitis C with sustained virologic response after antiviral treatment. During study enrollment, advanced liver fibrosis was operationally defined as a FibroScan liver stiffness measurement of at least 9.5 kPa. The non-advanced fibrosis comparison cohort was defined by a liver stiffness measurement of less than 6.0 kPa.
ACTUAL ENROLLMENT AND FOLLOW-UP
The study was originally planned to enroll 120 participants in the four randomized groups and an additional 30 participants in the non-randomized comparison cohort.
Recruitment began in January 2024. The study and recruitment period was subsequently extended through December 2025 with formal Institutional Review Board approval. Despite the approved extension, recruitment remained substantially slower than anticipated, and the available study funding was exhausted before the planned sample size could be reached. Recruitment was therefore discontinued, and the study was terminated early.
The final actual enrollment was 19 participants. Thirteen participants with presumed advanced fibrosis were randomized. One participant assigned to the UDCA group was subsequently excluded from the final analyses because the advanced-fibrosis eligibility criteria were not confirmed during post-randomization review. This participant remained included in the actual enrollment count.
The final analysis set therefore included 18 eligible participants: 12 participants with advanced fibrosis, with three participants in each randomized group, and six participants with non-advanced fibrosis in the non-randomized comparison cohort.
Baseline blood and stool samples were collected from all enrolled participants. Samples from the participant whose eligibility was not confirmed were excluded from the final analyses. Six-month follow-up samples were collected from the nine participants in the three active-treatment groups. The observation group and the non-advanced fibrosis comparison group contributed baseline data only.
STUDY ASSESSMENTS
Study assessments included clinical characteristics, stool microbiota profiles, targeted fecal bile acid measurements, inflammatory markers, and fibrosis-related biomarkers.
Microbiota assessments included measures of microbial diversity and taxonomic composition. Fecal bile acid assessments included selected primary, secondary, and conjugated bile acids. Changes from baseline to six months were evaluated in participants receiving active treatment.
Because of the small number of participants and the absence of longitudinal sampling in the observation and non-advanced fibrosis comparison groups, all treatment-related assessments were considered exploratory and hypothesis-generating. The study was not adequately powered to establish clinical efficacy, histological fibrosis regression, or superiority of one treatment regimen over another.
PROTOCOL NONCOMPLIANCE AND REGULATORY HANDLING
The operational liver-stiffness criterion applied during enrollment differed from the more restrictive fibrosis-related eligibility criteria specified in the original protocol and initial ClinicalTrials.gov record. Consequently, some participants included in the operationally defined advanced-fibrosis cohort did not meet the original fibrosis-related eligibility definition.
This protocol noncompliance was formally reported to the Institutional Review Board and was acknowledged on June 8, 2026 (IRB protocol no. 202201398A3; noncompliance report no. 202201398A3C2001). The Institutional Review Board subsequently accepted the study closure report on July 23, 2026.
The results of this prematurely terminated pilot study should therefore be interpreted as exploratory biological observations rather than confirmatory evidence of treatment efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- This is a randomized, controlled, parallel-group study with four arms. Eligible participants with advanced liver fibrosis are randomly assigned in a 1:1:1:1 ratio to receive either (1) no treatment (control), (2) ursodeoxycholic acid (UDCA) alone, (3) simvastatin alone, or (4) a combination of simvastatin and UDCA for 6 months. Randomization is performed using block randomization to ensure balanced allocation across groups. The groups are followed in parallel, and no crossover occurs between arms. A separate healthy control group (non-cirrhotic) provides baseline microbiota and bile acid profile comparisons but is not included in the interventional randomization.
| Arm | Type | Receives |
|---|---|---|
| Advanced liver fibrosis -Control Group | No intervention | –Participants receive standard clinical monitoring without any investigational treatment. No simvastatin or ursodeoxycholic acid (UDCA) is administered during the 6-month study period. |
| Advanced liver fibrosis -UDCA Group | Experimental | Drug: Ursodeoxycholic Acid (URSO)Participants receive ursodeoxycholic acid (UDCA) at a dose of 10 mg/kg/day orally for 6 months to evaluate its effect on liver fibrosis, bile acid metabolism, and gut microbiota. |
| Advanced liver fibrosis -Simvastatin Group | Experimental | Drug: SimvastatinParticipants receive simvastatin at a dose of 40 mg/day orally for 6 months. The treatment aims to assess effects on fibrosis markers, inflammation, and gut microbiota composition. |
| Advanced liver fibrosis -Simvastatin + UDCA Group | Experimental | Drug: Ursodeoxycholic Acid (URSO), Drug: SimvastatinParticipants receive a combination of simvastatin (40 mg/day) and ursodeoxycholic acid (UDCA) (10 mg/kg/day) orally for 6 months. The combination therapy is evaluated for potential synergistic effects on fibrosis reduction, bile acid modulation, and microbiota restoration. |
| Non-advanced Fibrosis Comparison Cohort | No intervention | –Participants without advanced fibrosis were enrolled as a non-randomized cohort for baseline comparison. No study medication was administered. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults aged 18 to 75 years
- Diagnosed with advanced fibrosis; the cohort was operationally defined by a FibroScan liver stiffness measurement of ≥9.5 kPa.
- Achieved sustained virological response (SVR) at least 6 months after hepatitis C treatment, or
- Non-replicating hepatitis B infection (undetectable viral load) for at least 6 months
- Able and willing to provide informed consent
Key exclusion criteria (10 listed)
- Current or prior use of statins
- Liver decompensation (jaundice, ascites, hepatic coma, or esophagogastric varices)
- Diagnosed hepatocellular carcinoma or other liver cancers
- Alcoholic liver disease or moderate-to-severe fatty liver
- Diagnosed diabetes mellitus
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 |
|---|---|---|
| Ursodeoxycholic Acid (URSO)Ursodeoxycholic acid (UDCA) was administered orally at a dose of 10 mg/kg/day for 6 months. | Drug | Advanced liver fibrosis -Simvastatin + UDCA Group, Advanced liver fibrosis -UDCA Group |
| SimvastatinSimvastatin was administered orally at a dose of 40 mg/day for 6 months. | Drug | Advanced liver fibrosis -Simvastatin + UDCA Group, Advanced liver fibrosis -Simvastatin Group |
Primary outcome
Change in liver fibrosis biomarker (TGF-β1)
Time frame: Baseline and 6 months after treatment initiation
Measurement of serum fibrosis-related marker TGF-β1. This will assess the antifibrotic effects of simvastatin, UDCA, and their combination in patients with stable liver cirrhosis.
Change in liver fibrosis biomarker (Type IV collagen)
Time frame: Baseline and 6 months after treatment initiation
Measurement of serum fibrosis-related marker Type IV collagen. This will assess the antifibrotic effects of simvastatin, UDCA, and their combination in patients with stable liver cirrhosis.
2 secondary outcomes
Change in Cirrhosis Dysbiosis Ratio (CDR)
Time frame: Baseline and 6 months after treatment
Change in Serum Inflammatory Cytokines
Time frame: Baseline and 6 months after treatment
Results and safety
The study was stopped early (reason given: Slow recruitment and exhaustion of available study funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Results publication: PubMed 21839040Islam KB, Fukiya S, Hagio M, Fujii N, Ishizuka S, Ooka T, Ogura Y, Hayashi T, Yokota A. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011 Nov;141(5):1773-81. doi: 10.1053/j.gastro.2011.07.046. Epub 2011 Aug 10.
- Results publication: PubMed 21574172Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011 Aug;54(2):562-72. doi: 10.1002/hep.24423. Epub 2011 Jun 26.
- Results publication: PubMed 22821944Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, Monteith P, Noble NA, Sikaroodi M, Gillevet PM. Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol. 2012 Sep 15;303(6):G675-85. doi: 10.1152/ajpgi.00152.2012. Epub 2012 Jul 19.
- Results publication: PubMed 21940902Bajaj JS, Ridlon JM, Hylemon PB, Thacker LR, Heuman DM, Smith S, Sikaroodi M, Gillevet PM. Linkage of gut microbiome with cognition in hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G168-75. doi: 10.1152/ajpgi.00190.2011. Epub 2011 Sep 22.
- Individual participant dataSharing planned: No. Individual Participant Data (IPD) will not be shared due to privacy concerns and data protection regulations. The study does not have participant consent or institutional approval for public data sharing. Aggregated results will be reported in scientific publications.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ursodeoxycholic Acid (URSO) and Simvastatin in people with Liver Fibrosis, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
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 5 inclusion and 10 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: stopped early, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
The study was stopped early (reason given: Slow recruitment and exhaustion of available study funding.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in liver fibrosis biomarker (TGF-β1) (time frame: Baseline and 6 months after treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07102979, which also lists 4 linked publications.
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 6 Aug 2026.