Fuzhenghuayu in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis

Ursodeoxycholic acid (UDCA) has been the only treatment for PBC approved by US and European drug administrations. Long-term use of UDCA (13-15 mg/kg/day) in patients with PBC improves serum liver biochemistries and survival free of liver transplantation.

However, about 40% of patients do not respond to UDCA optimally as assessed by known criteria for biochemical response. Those patients represent the group in need for additional therapies, having increased risk of disease progression and decreased survival free of liver transplantation. And UDCA has less effect on PBC patients whose pathology stage 3-4. Liver fibrosis might jeopardize the UDCA effect. Fuzhenghuayu is a Chinese traditional medicine for liver fibrosis and cirrhosis. Both lab research and some clinical studies suggest that Fuzhenghuayu could significantly reverse liver fibrosis and cirrhosis due to different kind of etiology. Here the investigators start a random, open and parallel clinical research to explore the effect of Fuzhenghuayu combined with UDCA in the PBC treatment.

Study Overview

• Status: Unknown
• Conditions: Primary Biliary Cirrhosis
• Intervention / Treatment: Drug: UDCA; Drug: Fuzhenghuayu

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hosipital of Digestive Disease
      • Contact: Ying Han, Ph.D; Phone Number: 86-29-84771539; Email: hanying@fmmu.edu.cn
      • Contact: Yongquan Shi, Ph.D; Phone Number: 86-29-84771515; Email: shiyquan@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent

2. Patient with PBC defined by 2 in 3 of the following criteria:

   • Positive antimitochondrial antibody type M2;
   • Abnormal serum alkaline phosphatases (ALP > 1,5N) and aminotransferase (AST or ALT > 1N) activities;
   • Histological hepatic injuries consistent with PBC.

Exclusion Criteria:

1. Pregnancy or desire of pregnancy.
2. Breast-feeding.
3. Co-existing liver diseases such as acute or chronic viral hepatitis, alcoholic liver disease, choledocholithiasis, autoimmune hepatitis, biopsy-proven non-alcoholic fatty liver disease, Wilson's disease and hemochromatosis.
4. History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
5. History of urolithiasis, nephritis or renal failure (clearance of creatinine < 60 ml/mn).
6. Hepatotoxic drugs use before recruiting.
7. Fuzhenghuayu anaphylaxis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fuzhenghuayu+UDCA; Regular UDCA treatment combination with Fuzhenghuayu	Drug: UDCA; Drug: Fuzhenghuayu
Active Comparator: Monotherapy; UDCA monotherapy	Drug: UDCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with complete biochemical response	Normalization of alkaline phosphatase (ALP) or decrease of ALP by more than 40% compared to the baseline.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver biopsy examinations compared to the baseline.	Histological evolution will be checked by liver biopsy at the end of the study to compare with baseline histological status.	Week 48
GLOBE scores.	The prognostic scores will be calculated at end of the study by GLOBE scoring system.	Week 48
Change in liver stiffness status measured by magnetic resonance elastography.	The change of liver stiffness status at the end of the study compared to baseline checked by magnetic resonance elastography.	Week 48
Change in serum alkaline phosphatase (ALP) level	Change in serum levels of ALP (IU/L) compared to the baseline.	Weeks 0, 4, 8, 12, 24, and 48
Change in serum bilirubin level	Change in serum levels of bilirubin (mg/dL) compared to the baseline	Weeks 0, 4, 8, 12, 24, and 48
Change in serum transaminase level	Change in serum levels of transaminase (IU/L) compared to the baseline.	Weeks 0, 4, 8, 12, 24, and 48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pruritus from baseline	The symptom of pruritus will be evaluated by questionnaire before enrollment and at the end of the study.	Week 48
Change in fatigue from baseline	The symptom of fatigue will be evaluated by Fatigue Impact Scale before enrollment and at the end of the study.	Week 48
Change in serum Immunoglobulin M Levels	Change in serum levels of Immunoglobulin M (g/L) compared to the baseline.	Week 48

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: January 28, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimate): September 27, 2016

Study Record Updates

• Last Update Posted (Estimate): September 27, 2016
• Last Update Submitted That Met QC Criteria: September 26, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Fuzhenghuayu
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: KY20151230-6