Clinical Research of UCDA Reducing Medication Regimen in Stable PBC

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Research of Reducing Medication Regimen for Ursodeoxycholic Acid in Treatment of Stable Primary Biliary Cholangitis

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: ursodeoxycholic acid


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ursodeoxycholic acid 250mg bid<br>Patients will receive a reduced dosage of ursodeoxycholic acid 250mg orally twice a day. | Drug: ursodeoxycholic acid<br>* 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 treatment duration will be five years.<br>* Other names: UDCA;|
| Experimental: ursodeoxycholic acid 250mg qd<br>Patients will receive a reduced dosage of ursodeoxycholic acid 250mg orally once a day. | Drug: ursodeoxycholic acid<br>* 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 treatment duration will be five years.<br>* Other names: UDCA;|
| Active Comparator: ursodeoxycholic acid standard dosage<br>Patients will receive standard dosage of ursodeoxycholic acid 250mg orally three times a day. | Drug: ursodeoxycholic acid<br>* 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 treatment duration will be five years.<br>* Other names: UDCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence rate of primary biliary cholangitis | 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. | change from baseline to month3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ursodeoxycholic acid, reducing medication regimen