Effect of Candesartan in Alcoholic Liver Fibrosis

Sponsor

Yonsei University (Other)

Overall Status

Completed

CT.gov ID

NCT00990639

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

Alcohol is one of principal causes of hepatic fibrosis. Although the most effective treatment for alcoholic hepatic fibrosis is abstinence of alcohol consumption, additive treatment to reduce the accumulation of scar tissue can accelerate the improvement of hepatic fibrosis in alcoholic liver disease. The renin-angiotensin system can be an attractive antifibrotic target in liver. Several lines of evidence indicate that overproduction of angiotensin II(ANG

in chronic liver injury stimulates the activation of hepatic stellate cells(HSCs) attributed to fibrogenesis. Additionally, the antifibrotic effect of ANG II blocking agent has been shown in various animal models and hepatitis C patients. Hence, drugs that inhibit the renin-angiotensin system have promise in ameliorating hepatic fibrosis in chronic liver injury. However, no study has been conducted in patients with alcoholic liver disease to evaluate the effect ANG II type I receptor blocking agent on hepatic fibrosis.

Aim:

This study aimed to investigate the safety and the efficacy of chronic administration of candesartan to hepatic fibrosis patients with alcoholic liver disease.

Methods

Patients with liver fibrosis(F2) were randomized to receive either the angiotensin receptor blocker(ARB), candesartan(8 mg/day) with ursodeoxycholic acid(UDCA)(600 mg/day)(n = 42), or UDCA alone(n = 43) as control for 6 months. 2)All enrolled patients underwent liver biopsies twice for measurement of fibrosis score, area of fibrosis and alpha-smooth muscle actin(SMA) positive and hydroxyproline. 3) Transforming growth factor-beta1(TGF-beta1), collagen-1, angiotensin II type I receptor(AT1-R), tissue inhibitor of metalloproteinase-1(TIMP-1), Rac1 and p22phox which represent oxidant stress were also measured by real-time RT-PCR before and after 6 months of therapy.

Condition or Disease	Intervention/Treatment	Phase
Alcoholic Liver Disease	Drug: candesartan for hepatic fibrosis	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Beneficial Effect of Angiotensin-blocking Agent Candesartan on Alcoholic Liver Fibrosis: A Randomized Controlled Trial

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: candesartan+UDCA group oral candesartan(8 mg/day) in addition to ursodeoxycholic acid (UDCA, 600 mg/day) for 6 months	Drug: candesartan for hepatic fibrosis Candesartan group(42 patients): oral candesartan at a daily dose of 8 mgin addition to ursodeoxycholic acid (UDCA, 600 mg/day) for 6 months. UDCA group(43 patients): oral ursodeoxycholic acid (UDCA, 600 mg/day) only for 6 months Other Names: atacand for hepatic fibrosis
Placebo Comparator: UDCA group ursodeoxycholic acid(UDCA,600 mg/day)only for 6 months	Drug: candesartan for hepatic fibrosis Candesartan group(42 patients): oral candesartan at a daily dose of 8 mgin addition to ursodeoxycholic acid (UDCA, 600 mg/day) for 6 months. UDCA group(43 patients): oral ursodeoxycholic acid (UDCA, 600 mg/day) only for 6 months Other Names: atacand for hepatic fibrosis

Arm

Intervention/Treatment

Experimental: candesartan+UDCA group

oral candesartan(8 mg/day) in addition to ursodeoxycholic acid (UDCA, 600 mg/day) for 6 months

Drug: candesartan for hepatic fibrosis

Candesartan group(42 patients): oral candesartan at a daily dose of 8 mgin addition to ursodeoxycholic acid (UDCA, 600 mg/day) for 6 months. UDCA group(43 patients): oral ursodeoxycholic acid (UDCA, 600 mg/day) only for 6 months

Other Names:

atacand for hepatic fibrosis

Placebo Comparator: UDCA group

ursodeoxycholic acid(UDCA,600 mg/day)only for 6 months

Drug: candesartan for hepatic fibrosis

Other Names:

atacand for hepatic fibrosis

Outcome Measures

Primary Outcome Measures

Improvement of histologic grade of hepatic fibrosis [6 month later]

Secondary Outcome Measures

estimation of safety of candesartan in hepatic fibrosis [6 month later]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Clinical diagnosis of alcoholic liver disease
METAVIR fibrosis score ≥ 2 in liver biopsy
Alcohol intake has stop during at least 6 months until study enrollment

Exclusion Criteria:

Hepatocellular carcinoma or other malignancy
Clinically decompensated cirrhosis (Total bilirubin ≥ 5mg/dL or variceal hemorrhage or ascites development or hepatic encephalopathy developement)
Chronic liver disease related with other causes except alcohol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yonsei University Wonju College of Medicine Wonju Christian Hospital	Wonju	Kangwon-do	Korea, Republic of	220-701

Sponsors and Collaborators

Yonsei University

Investigators

Principal Investigator: Soon Koo Baik, Professor, Yonsei University Wonju College of Medicine Department of Internal Medicine Devision of Gastroenterology and Hepatology