Back to results

Pentoxifylline for Primary Biliary Cirrhosis

Primary Purpose

Primary Biliary Cirrhosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Pentoxifylline

About this trial

This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring biliary cirrhosis

Eligibility Criteria

18 Years - 76 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male and female patients ages 18 to 76 years.
Established diagnosis of PBC based on at least three of the following criteria:
- Detectable anti-mitochondrial antibodies (AMA)
- Cholestatic biochemical pattern
- Liver biopsy compatible with PBC
- Appropriate exclusion of other liver diseases.
Therapy with UDCA at adequate dose (13-15mg/kg/d) for at least six months and evidence of suboptimal response defined by alkaline phosphatase levels that did not normalize and remain elevated by at least 1.5 times the upper limit of normal.
No history or present hepatic decompensation (e.g. variceal hemorrhage, encephalopathy, or poorly controlled ascites).

Exclusion Criteria:

Findings highly suggestive of liver disease of other etiology.
A score >=10 points on the Revised Scoring System for autoimmune hepatitis (AIH), supporting a diagnosis of PBC/AIH overlap.
Patients on steroids (systemic), immunosuppressants, or immunomodulatory agents within the previous 6 months.
Patients with clinical or laboratory evidence suggestive of decompensated cirrhosis.
Hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, theobromine).
History of cerebral or retinal hemorrhage.
Other medical comorbidities (such as cardiac, renal, cancer) that would interfere with completion of the study.
Patients taking Theophylline or Coumadin because of potential drug-drug interactions with PTX. In addition, patients taking low molecular weight heparin preparations.
Pregnant or nursing women.

Sites / Locations

Cleveland Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pentoxifylline 400 mg TID

Arm Description

This study is an open label pilot with only one arm.

Outcomes

Primary Outcome Measures

Change in Serum Alkaline Phosphatase Levels.

Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared.

Secondary Outcome Measures

Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy.

Serum concentration of tissue inhibitor metalloproteinase 1 (TIMP-1), a fibrosis biomarker of interest, will be measured and the change in serum levels between entry and end of study will be calculated.

Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed

The number of participants that experienced any severe adverse events will be monitored and recorded.

Full Information

NCT ID

NCT01249092

First Posted

November 24, 2010

Last Updated

October 16, 2013

Sponsor

The Cleveland Clinic

1. Study Identification

Unique Protocol Identification Number

NCT01249092

Brief Title

Pentoxifylline for Primary Biliary Cirrhosis

Official Title

A Pilot Study of Pentoxifylline for the Treatment of Primary Biliary Cirrhosis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2013

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

June 2012 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Cleveland Clinic

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Primary biliary cirrhosis (PBC) is cholestatic liver disease characterized by progressive destruction of small bile ducts within the liver that can lead to end stage liver disease and all its complications. Although ursodeoxycholic acid (UDCA) is associated with increased survival in many patients with PBC, there is absence of an adequate response to UDCA in a significant proportion of PBC patients. Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays an important role in the pathogenesis of PBC. Other fibrosis biomarkers such as tissue metallo proteinase 1 (TIMP-1) are associated with progression of liver fibrosis in PBC. Pentoxifylline (PTX) is a methylxanthine derivative that inhibits pro-inflammatory cytokines and also has shown anti-fibrotic effects in serum of patients with PBC. Furthermore, PTX has well known clinical and safety profiles. The main hypothesis of this study is that therapy with pentoxifylline (PTX) will result in improvement of liver disease in PBC patients who are incomplete responders to UDCA. The focus of this proposal is on the effectiveness of PTX in improving laboratory parameters of liver disease and levels of cytokines involved in the pathogenesis of the disease in patients with PBC.

6. Conditions and Keywords

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

Primary Biliary Cirrhosis

Keywords

biliary cirrhosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pentoxifylline 400 mg TID

Arm Type

Experimental

Arm Description

This study is an open label pilot with only one arm.

Intervention Type

Drug

Intervention Name(s)

Pentoxifylline

Intervention Description

Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.

Primary Outcome Measure Information:

Title

Change in Serum Alkaline Phosphatase Levels.

Description

Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared.

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy.

Description

Time Frame

6 months

Title

Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed

Description

The number of participants that experienced any severe adverse events will be monitored and recorded.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

76 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and female patients ages 18 to 76 years. Established diagnosis of PBC based on at least three of the following criteria: Detectable anti-mitochondrial antibodies (AMA) Cholestatic biochemical pattern Liver biopsy compatible with PBC Appropriate exclusion of other liver diseases. Therapy with UDCA at adequate dose (13-15mg/kg/d) for at least six months and evidence of suboptimal response defined by alkaline phosphatase levels that did not normalize and remain elevated by at least 1.5 times the upper limit of normal. No history or present hepatic decompensation (e.g. variceal hemorrhage, encephalopathy, or poorly controlled ascites). Exclusion Criteria: Findings highly suggestive of liver disease of other etiology. A score >=10 points on the Revised Scoring System for autoimmune hepatitis (AIH), supporting a diagnosis of PBC/AIH overlap. Patients on steroids (systemic), immunosuppressants, or immunomodulatory agents within the previous 6 months. Patients with clinical or laboratory evidence suggestive of decompensated cirrhosis. Hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, theobromine). History of cerebral or retinal hemorrhage. Other medical comorbidities (such as cardiac, renal, cancer) that would interfere with completion of the study. Patients taking Theophylline or Coumadin because of potential drug-drug interactions with PTX. In addition, patients taking low molecular weight heparin preparations. Pregnant or nursing women.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Claudia O. Zein, MD, MSc

Organizational Affiliation

The Cleveland Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Pentoxifylline for Primary Biliary Cirrhosis

We'll reach out to this number within 24 hrs