Effect of Candesartan in Alcoholic Liver Fibrosis

This study has been completed.
Sponsor:
Information provided by:
Yonsei University
ClinicalTrials.gov Identifier:
NCT00990639
First received: October 6, 2009
Last updated: NA
Last verified: October 2009
History: No changes posted
  Purpose

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 II) 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

1) 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 Intervention Phase
Alcoholic Liver Disease
Drug: candesartan for hepatic fibrosis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Beneficial Effect of Angiotensin-blocking Agent Candesartan on Alcoholic Liver Fibrosis: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Yonsei University:

Primary Outcome Measures:
  • Improvement of histologic grade of hepatic fibrosis [ Time Frame: 6 month later ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • estimation of safety of candesartan in hepatic fibrosis [ Time Frame: 6 month later ] [ Designated as safety issue: Yes ]

Enrollment: 85
Study Start Date: September 2005
Study Completion Date: March 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: atacand for hepatic fibrosis

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00990639

Locations
Korea, Republic of
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
  More Information

Publications:
Responsible Party: Soon Koo Baik/ Yonsei University Wonju College of Medicine Department of Internal Medicine Devision of Gastroenterology and Hepatology, Yonsei University Wonju College of Medicine Department of Internal Medicine Devision of Gastroenterology and Hepatology
ClinicalTrials.gov Identifier: NCT00990639     History of Changes
Other Study ID Numbers: YWhep091
Study First Received: October 6, 2009
Last Updated: October 6, 2009
Health Authority: Korea: Institutional Review Board
Korea: Food and Drug Administration

Keywords provided by Yonsei University:
hepatic fibrosis
angiotensin II blocking agents
alcoholic liver disease

Additional relevant MeSH terms:
Fibrosis
Liver Diseases
Liver Diseases, Alcoholic
Liver Cirrhosis
Pathologic Processes
Digestive System Diseases
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Ursodeoxycholic Acid
Candesartan
Candesartan cilexetil
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014