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Moexipril for Primary Biliary Cirrhosis

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. Identifier: NCT00588302
Recruitment Status : Completed
First Posted : January 8, 2008
Last Update Posted : May 23, 2011
UCB Pharma
Information provided by:
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE December 22, 2007
First Posted Date  ICMJE January 8, 2008
Last Update Posted Date May 23, 2011
Study Start Date  ICMJE June 2003
Actual Primary Completion Date June 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2007)
change in liver biochemistries and Mayo risk score for PBC [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2007)
change in health-related quality of life in PBC [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Moexipril for Primary Biliary Cirrhosis
Official Title  ICMJE Open-Label Pilot Investigation of Moexipril for the Treatment of Primary Biliary Cirrhosis (PBC)
Brief Summary The blockade of angiotensin II synthesis attenuates hepatic fibrosis in different experimental models of chronic liver injury. We aimed to determine the safety and efficacy of moexipril, an angiotensin-converting enzyme (ACE) inhibitor, on liver biochemistries, Mayo risk score, and health-related quality of life in patients with primary biliary cirrhosis (PBC) who have had a suboptimal response to ursodeoxycholic acid (UDCA).
Detailed Description

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune cause characterized by progressive inflammatory destruction of interlobular and septal bile ducts, resulting in fibrosis and eventual cirrhosis (1). In PBC patients, the most disabling symptoms are fatigue and pruritus which diminish health-related quality of life (HRQL. Ursodeoxycholic acid (UDCA), at a dose of 13 to 15 mg/kg per day, is a safe and effective medical therapy for most patients with PBC. Nevertheless, UDCA therapy has not ameliorated symptoms associated with PBC. Some UDCA-treated patients show progressive disease resulting in the liver transplantation or death from liver-related causes. For these patients, who show a persistent elevation of serum alkaline phosphatase at least twice the normal level after 6 months of UDCA monotherapy (incomplete responders), the evaluation of combination therapy in clinical trials has been recommended.

Moexipril is a long-acting, nonsulfhydryl ACE inhibitor with lipophilicity, and so can readily penetrate lipid membranes and thus target tissue ACE in addition to plasma ACE. This drug also demonstrated antioxidative properties in addition to efficiently controlling blood pressure in hypertensive postmenopausal subjects. Moreover, quality-of-life data suggest favorable effects of moexipril treatment in a patient population at high cardiovascular risk. The tolerability and safety profile of moexipril resembles that of other ACE inhibitors along with no reports of hepatotoxicity in controlled trials. Hence, moexipril is an attractive drug for evaluation in patients with chronic liver disease.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Primary Biliary Cirrhosis
Intervention  ICMJE Drug: Moexipril
Moexipril was given at a starting dose of 7.5 mg daily for 1 week to all enrolled patients. If tolerated (no clinically significant hypotension or medication associated adverse event), the daily dosage was increased to 15 mg daily at the beginning of the 2nd treatment week. Patients took moexipril orally in the morning and 1 hour prior to food intake. The target dose was maintained for the 1-year period of the study unless the development of toxicities warranted dose reduction or discontinuation.
Study Arms  ICMJE Experimental: A, 1
All patients received an open-label moexipril during the study period.
Intervention: Drug: Moexipril
Publications * Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003 Jul 5;362(9377):53-61. Review.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 22, 2007)
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2007
Actual Primary Completion Date June 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • PBC patients treated with UDCA (daily dose of 13 to 15 mg/kg for at least 6 months) and an incomplete response defined by persistent elevation of serum alkaline phosphatase activity at least 2 times the upper limit of normal

Exclusion Criteria:

  • age less than 18 years
  • pregnancy or nursing
  • anticipated need for liver transplantation within 1 year with less than a 80% one-year survival determined by the Mayo risk score
  • complications of cirrhosis such as recurrent variceal hemorrhage, portosystemic encephalopathy, and refractory ascites
  • history of coexistent severe cardiovascular disease including aortic stenosis
  • history of coexistent severe renal disease (defined as elevation of serum creatinine more than 1.5 mg/dL) including renal artery stenosis
  • history of allergy to ACE inhibitors
  • current use of an ACE inhibitors or AT1 receptor antagonists in the past 3 months
  • previous treatment with immunosuppressive agents or any experimental drug in the preceding 3 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00588302
Other Study ID Numbers  ICMJE 1032-03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE UCB Pharma
Investigators  ICMJE
Principal Investigator: Keith D Lindor, MD Mayo Clinic and Foundation
PRS Account Mayo Clinic
Verification Date May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP