Remedial Mechanism of Simvastatin and Ursodeoxycholic Acid in Liver Cirrhosis: Crosstalk of Bile Secretion, Gut Microbiome, and Host Immune Response

NCT07102979 | Enrolling By Invitation DMC

• 2 other identifiers: IRB 202201398A3CMRPG8P0291
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn whether simvastatin alone or in combination with ursodeoxycholic acid (UDCA) can reduce liver fibrosis, inflammation, and gut microbiota imbalance in patients with liver cirrhosis who have achieved viral eradication after hepatitis C or inactive hepatitis B. The main questions the study aims to answer are: Can simvastatin or UDCA reduce biomarkers of liver fibrosis and chronic inflammation? Do these treatments improve gut microbiota composition and bile acid metabolism? Is combination therapy more effective than either drug alone? In this study, 120 patients with stable liver cirrhosis will be randomly assigned to one of four groups: no treatment (control), UDCA alone, simvastatin alone, or simvastatin plus UDCA. Patients will be followed for 6 months, during which stool, blood, and skin samples will be collected to assess gut microbiota, bile acid profiles, inflammatory markers, and fibrosis indicators. A group of 30 healthy individuals without cirrhosis will also provide baseline comparisons for microbiota and bile acid profiles.

Conditions

Liver Cirrhosis

Keywords

liver cirrhosis; fecal bile salt; UDCA; statin

Outcome Measures

Primary Outcomes (4)

• 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.

  Baseline and 6 months after treatment initiation

• Change in liver fibrosis biomarker (Type IV collage)

  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.

  Baseline and 6 months after treatment initiation

• Change in liver fibrosis biomarker (Hyaluronic Acid)

  Measurement of serum fibrosis-related marker Hyaluronic Acid. This will assess the antifibrotic effects of simvastatin, UDCA, and their combination in patients with stable liver cirrhosis.

  Baseline and 6 months after treatment initiation

• Change in liver fibrosis biomarker (FIB-4 Index)

  Measurement of serum fibrosis-related marker FIB-4 Index.. This will assess the antifibrotic effects of simvastatin, UDCA, and their combination in patients with stable liver cirrhosis.

  Baseline and 6 months after treatment initiation

Secondary Outcomes (3)

• Change in Cirrhosis Dysbiosis Ratio (CDR)

  Baseline and 6 months after treatment

• Change in Serum Inflammatory Cytokines

  Baseline and 6 months after treatment

• Change in Skin Bile Acid Profile

  Baseline and 6 months after treatment

Study Arms (4)

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.

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.

Drug: Simvastatin

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.

Drug: Ursodeoxycholic Acid (URSO)

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.

Drug: Ursodeoxycholic Acid (URSO); Drug: Simvastatin

Interventions

Ursodeoxycholic Acid (URSO) DRUG

Ursodeoxycholic acid (UDCA) was administered orally at a dose of 10 mg/kg/day for 6 months.

Simvastatin + UDCA Group; Simvastatin Group

Simvastatin DRUG

Simvastatin was administered orally at a dose of 40 mg/day for 6 months.

Simvastatin + UDCA Group; UDCA Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 75 years
• Diagnosed with primary liver cirrhosis (FIB-4 ≥ 3.25)
• Liver stiffness measurement (LSM) ≥ 25 kPa, or classified into the Baveno VII "grey zone"
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Others, 833, Taiwan

Location

Related Publications (4)

• 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.

  PMID: 21839040 RESULT

• Chen 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.

  PMID: 21574172 RESULT

• Bajaj 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.

  PMID: 22821944 RESULT

• Bajaj 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.

  PMID: 21940902 RESULT

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Ursodeoxycholic Acid; Simvastatin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study. No participants, investigators, or outcome assessors are masked to treatment allocation. All parties involved are aware of the assigned interventions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, controlled, parallel-group study with four arms. Eligible participants with stable liver cirrhosis 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.

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 5, 2025
• Study Start: September 1, 2025
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)