Clinical Research of Tapering UDCA in PBC Patients with a Complete Response (UDCA PBC)

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 4

Conditions: Primary Biliary Cholangitis

Treatments: Drug: ursodeoxycholic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT04650243

ZS-2237

Details and patient eligibility

About

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.

Full 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 PBC patients with a complete response will be distributed randomly into two experimental groups and one control group. The two experimental groups will receive reduced dosage of UDCA at 10mg/Kg and 5mg/Kg respectively, while the control group will receive standard 13-15mg/Kg 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Satisfied the diagnostic criteria of PBC by the AASLDin 2000;
• Age≥18 years
• Clinical stage 2 and 3 (i.e. abnormal liver function and symptomatic phase);
• Patients with improved liver biochemical index( ALP and AST≤1.5× upper limit of normal, with a normal bilirubin level) after 6 to 12 months treatment of UDCA;
• Informed consent obtained.

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);
• 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.;
• Participating in other clinical trials or participated in other clinical trials in three months.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

10mg/Kg UDCA

Experimental group

Description:

Patients will receive a reduced dosage of 10mg/Kg UDCA orally everyday.

Treatment:

Drug: ursodeoxycholic acid

5mg/Kg UDCA

Experimental group

Description:

Patients will receive a reduced dosage of 5mg/Kg UDCA orally everyday.

Treatment:

Drug: ursodeoxycholic acid

standard 13-15mg/Kg UDCA

Active Comparator group

Description:

Patients will receive standard dosage of 13-15mg/Kg UDCA everyday.

Treatment:

Drug: ursodeoxycholic acid