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

Primary Purpose

Hepatitis C

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Candesartan
Placebo
Sponsored by
Kaiser Permanente
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kaiser Permanente
  • Kaiser Permanente

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

A

B

Arm Description

Outcomes

Primary Outcome Measures

Primary: • Stellate cell activity by alpha SMA stain quantitated by morphometry
• Hepatic fibrosis by morphometry

Secondary Outcome Measures

Surrogate markers for fibrosis (liver TGF-beta levels, serum procollagen-III peptide levels)
Functional status- Albumin, INR, T. Bilirubin, MELD score

Full Information

First Posted
July 1, 2009
Last Updated
April 23, 2012
Sponsor
Kaiser Permanente
Collaborators
University of California, Davis
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1. Study Identification

Unique Protocol Identification Number
NCT00930995
Brief Title
Angiotensin Receptor Blockade as an Anti-Fibrotic Intervention in Patients With Chronic Hepatitis C
Official Title
Angiotensin Receptor Blockade an Anti-Fibrotic Intervention in Patients With Chronic Hepatitis C
Study Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Not Awarded
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Kaiser Permanente
Collaborators
University of California, Davis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Title
B
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Candesartan
Other Intervention Name(s)
Atacand
Intervention Description
16mg po daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
once daily
Primary Outcome Measure Information:
Title
Primary: • Stellate cell activity by alpha SMA stain quantitated by morphometry
Time Frame
48 weeks
Title
• Hepatic fibrosis by morphometry
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Surrogate markers for fibrosis (liver TGF-beta levels, serum procollagen-III peptide levels)
Time Frame
48 weeks
Title
Functional status- Albumin, INR, T. Bilirubin, MELD score
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sripriya Subramanian, MD, MPH
Organizational Affiliation
Kaiser Permanente
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kaiser Permanente
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Kaiser Permanente
City
Sacramento
State/Province
California
ZIP/Postal Code
95825
Country
United States

12. IPD Sharing Statement

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

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