Clinical trial NCT04650243: Clinical Research of Tapering UDCA in PBC Patients With a Complete Response
Official title: Clinical Research of Tapering Ursodeoxycholic Acid in Primary Biliary Cholangitis Patients With A Complete Response
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Primary Biliary Cholangitis
Keywords: ursodeoxycholic acid
reducing medication regimen
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-12-02
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 UDCA. The effect of therapy will be evaluated every three months.
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence rate of primary biliary cholangitis
timeFrame: change from baseline to month3,6,9,12.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
Study officials:
affiliation: Peking Union Medical College Hospital
name: Li Wang
role: STUDY_DIRECTOR
References: