Angiotensin Receptor Blockade as an Anti-Fibrotic Intervention in Patients With Chronic Hepatitis C

This study has been withdrawn prior to enrollment.
(Not Awarded)
Sponsor:
Collaborator:
University of California, Davis
Information provided by:
Kaiser Permanente
ClinicalTrials.gov Identifier:
NCT00930995
First received: July 1, 2009
Last updated: April 23, 2012
Last verified: April 2012
  Purpose

Hepatitis C is the most common reason for liver transplantation in the United States and affects nearly 4 million Americans. Treatments for hepatitis C are available but are poorly tolerated and are not always effective. Morbidity and mortality from hepatitis C are related to the development and progression of hepatic fibrosis to cirrhosis and end stage liver disease. Efforts to block progression of liver disease would thus result in prevention of morbidity and mortality as well as costs incurred by the health system in the care of these conditions.

Scar tissue in the liver is secreted by a type of cell, called the stellate cell, in an activated state. This cell carries a receptor for angiotensin, a hormone, when activated. If this receptor is blocked, the cell becomes inactive and does not participate in scar tissue formation. Thus, we hypothesize that using a drug such as candesartan, which blocks angiotensin receptors, should result in less scar tissue formation in the livers of patients with hepatitis C.


Condition Intervention Phase
Hepatitis C
Drug: Candesartan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Angiotensin Receptor Blockade an Anti-Fibrotic Intervention in Patients With Chronic Hepatitis C

Resource links provided by NLM:


Further study details as provided by Kaiser Permanente:

Primary Outcome Measures:
  • Primary: • Stellate cell activity by alpha SMA stain quantitated by morphometry [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • • Hepatic fibrosis by morphometry [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Surrogate markers for fibrosis (liver TGF-beta levels, serum procollagen-III peptide levels) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Functional status- Albumin, INR, T. Bilirubin, MELD score [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 0
Arms Assigned Interventions
Active Comparator: A Drug: Candesartan
16mg po daily
Other Name: Atacand
Placebo Comparator: B Drug: Placebo
once daily

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults, age 21 and older
  • Patients with viral hepatitis C that are not on interferon based therapy.
  • Detectable viral load
  • Baseline biopsy within six months or willing to undergo biopsy prior to drug initiation
  • At least grade 2 inflammation on biopsy, fibrosis of stage 1 or higher
  • Willing to undergo biopsy at the end of treatment
  • No interferon for at least 6 months prior to or after initial biopsy for study

Exclusion Criteria:

  • Renal impairment defined by a serum creatinine of >1.8
  • Congestive heart failure
  • Hepatocellular cancer
  • Concurrent treatment with pentoxyfylline, steroids, interferon alpha or interferon gamma.
  • Active psychosis (affective disorders without loss of reality testing acceptable)
  • Active IV drug use
  • Prior liver transplant
  • Pregnancy
  • Decompensated cirrhosis as defined by the presence of ascites, hepatic encephalopathy or coagulopathy with an INR>1.4
  • HIV seropositivity
  • Hypotension defined by a baseline systolic blood pressure of less than 90mm of mercury
  • Contraindication to ARB use or allergy to medication
  • Treatment with potassium sparing diuretics
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930995

Locations
United States, California
Kaiser Permanente
Roseville, California, United States, 95661
Kaiser Permanente
Sacramento, California, United States, 95825
Sponsors and Collaborators
Kaiser Permanente
University of California, Davis
Investigators
Principal Investigator: Sripriya Subramanian, MD, MPH Kaiser Permanente
  More Information

No publications provided

Responsible Party: Sripriya Balasubramanian MD MPH, Kaiser Permanente
ClinicalTrials.gov Identifier: NCT00930995     History of Changes
Other Study ID Numbers: CN-05SBala-01-B
Study First Received: July 1, 2009
Last Updated: April 23, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 29, 2014