We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Candesartan in Alcoholic Liver Fibrosis

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00990639
First Posted: October 7, 2009
Last Update Posted: October 7, 2009
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Yonsei University
  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
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

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 ]

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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
First Submitted: October 6, 2009
First Posted: October 7, 2009
Last Update Posted: October 7, 2009
Last Verified: October 2009

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

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