Clinical Research of UCDA Reducing Medication Regimen in Stable PBC

Phase 4

Recruiting

• Conditions: Primary Biliary Cholangitis
• Interventions: Drug: ursodeoxycholic acid

• Registration Number: NCT04650243
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

This study explores the feasibility of the reducing medication regimen for Ursodeoxycholic Acid(UDCA) in the treatment of primary biliary cholangitis. The participants will be distributed randomly into two experimental groups and one control group. The two experimental groups will receive reduced dosage of UDCA at different level, while the control group will receive standard dosage of UDCA. The effect of therapy will be evaluated every three months.

Detailed Description

Primary biliary cholangitis is a chronic, progressive liver disease of autoimmune origin characterized by nonpurulent destruction of intrahepatic ductule, lymphatic infiltration of portal area and long-term intrahepatic cholestasis leading to liver fibrosis and cirrhosis in absence of treatment. The diagnosis is made in the presence of antimitochondrial antibodies (AMA) coupled with an increase in alkaline phosphatase (ALP), a histologic confirmation being mandatory only in seronegative cases or overlap syndrome. Treatment is based on ursodeoxycholic acid (UDCA) and obeticholic acid, which are proved effective in improving biochemical index and preventing disease progression. While obeticholic acid is only approved in USA and Canada, UDCA seem to be the only choice for PBC patients in China. Study has shown that liver function improvement can be expected in six to nine months when patients receive standard dosage( 13 -15mg/kg/d) of UDCA. Recovery of liver function takes two years in 20% of patients ,and five years in 15% to 35% of patients. Lifetime medication is recommended among patients with good respond to UDCA, while the high cost has placed great burden on patients as well as the medical service system. Exploration of the reducing medication regimen of UDCA among stable PBC patients is of great significance under this circumstance. In our study, the 90 recruited patients of refractory PBC will be distributed randomly into two experimental groups and one control group. The two experimental groups will receive reduced dosage of UDCA at 250mg bid and 250mg qd respectively, while the control group will receive standard dosage of UDCA. The effect of therapy will be evaluated every three months, which includes assessment of symptoms, life quality, disease progression, complete blood count, urinalysis, liver biochemical markers (ALT, AST, ALP, GGT, TBIL, DBIL, TP, ALB), blood lipid (CHO, TG, LDL, HDL), immunoglobulins, ESR, AMA, liver morphology and cirrhosis degree, along with peripheral T lymphocyte subpopulations and cytokines test.

Study Timeline

• Study Start: 2020-03-21
• Study First Submitted: 2020-04-27
• Study First Submitted QC: 2020-11-30
• Study First Posted: 2020-12-02
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-28
• Last Update Posted: 2022-05-04
• Primary Completion: 2024-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

• Satisfied the diagnostic criteria of PBC by the AASLDin 2000;
• Aged 18-65 years old;
• Clinical stage 2 and 3 (i.e. abnormal liver function and symptomatic phase);
• Patients with improved liver biochemical index(i.e. bilirubin≤17μmol/L, ALP≤3ULN, and AST≤2ULN) for at least 6 months after 6 to 12 months treatment of UDCA;
• Informed consent obtained.

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Exclusion Criteria

• Overlapped with other liver diseases (such as HBV, HCV, alcoholic cirrhosis, etc.) or serum ALT, AST more than 2 ULN;
• Decompensation of liver function (Child grade B/C);
• Combined with other autoimmune diseases;
• Complicated with important organ failure (such as renal insufficiency), serious infection or other serious complications;
• Pregnancy, preparation for pregnancy or pregnancy Lactation, psychiatric subjects, etc.;
• Combined with tumor;
• Participating in other clinical trials or participated in other clinical trials in three months.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ursodeoxycholic acid 250mg bid	ursodeoxycholic acid	Patients will receive a reduced dosage of ursodeoxycholic acid 250mg orally twice a day.
ursodeoxycholic acid standard dosage	ursodeoxycholic acid	Patients will receive standard dosage of ursodeoxycholic acid 250mg orally three times a day.
ursodeoxycholic acid 250mg qd	ursodeoxycholic acid	Patients will receive a reduced dosage of ursodeoxycholic acid 250mg orally once a day.

Primary Outcome Measures

Name	Time	Method
Recurrence rate of primary biliary cholangitis	change from baseline to month3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60	Liver biochemical markers (AST and ALP in U/L, BIL in umol/L) that restored to normal increase(bilirubin\>17μmol/L,ALP\>3 ULM, AST\>2 ULN) again is considered to be PBC recurrence. The rate of recurrence will be described in percent.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China