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Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis (HAART)

Primary Purpose

Primary Biliary Cirrhosis

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Truvada and Kaletra

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

Patients 18 years old of either sex will be recruited for this study.
Elevated ALP after 6 months UDCA therapy ≥ 2 x upper limit of normal or abnormal bilirubin.
Positive serum AMA or Liver biopsy histology compatible with PBC.
Maintained on UDCA at a dose of 13-15 mg/kg for 6 or more months.
Patients must read and sign informed consent form

Exclusion Criteria:

Subjects with baseline AST or ALT > 5 x ULN.
Patients who have altered dose of any medications used to treat PBC (such as UDCA) or the use of colchicine, corticosteroids, azathioprine, chlorambucil, methotrexate, or D-penicillamine within the last 6 months.
Advanced liver disease or esophageal varices, INR > 1.2 (upper limit of normal), Albumin < 35 g/L (lower limit of normal), platelets < 120,000/mm3, Childs Pugh class B or C cirrhosis, presence of varices or previous variceal hemorrhage, spontaneous encephalopathy, ascites or need for liver transplantation.
Patients with a secondary diagnosis such as HIV, viral hepatitis, drug induced liver injury, extrahepatic biliary obstruction, primary sclerosing cholangitis, metabolic liver diseases or alcoholic liver disease Regular use of more than 30 g of alcohol per day in the last year. Clinically apparent pancreatitis or with a predicted survival of less than 3 years from malignant or other potentially life threatening disease.
An ultrasound showing a hepatic mass consistent with hepatocellular carcinoma within the last year in patients with cirrhosis.
Previous allergic reaction to study medications.
Creatinine clearance less than < 70 mL/min using the Cockcroft Gault equation:
Creatinine clearance (mL/min) = (140 - age) x body wt (Kg) x 0.85 (if female)/serum creatinine in mol/l
Pregnancy or breast-feeding a child. Young sexually active patients not using contraception
Young sexually active patients not using contraception.

Sites / Locations

University of Alberta

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Truvada and Kaletra

Arm Description

6 months therapy with blinded placebo followed by 6 months open label therapy with Kaletra and Truvada. Then there is an option for an 18 month follow-up study.

Patients will be take Truvada and Kaletra for 6 months with the option of open label for additional 18 months.

Outcomes

Primary Outcome Measures

Reduction of ALP to 1.67x ULN

normalization of bilirubin.

Secondary Outcome Measures

Reduction of human betaretrovirus.

Symptoms with changes in PBC-40

Changes in AMA and immunoglobulin levels

Biochemistry: GGT, AST and ALT

Histology in extension study

Full Information

NCT ID

NCT01614405

First Posted

April 25, 2011

Last Updated

November 30, 2015

Sponsor

University of Alberta

Collaborators

Abbott, Gilead Sciences, Canadian Institutes of Health Research (CIHR)

1. Study Identification

Unique Protocol Identification Number

NCT01614405

Brief Title

Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis

Acronym

HAART

Official Title

Randomized Controlled Pilot Study of Highly Active Anti-Retroviral Therapy for Patients With Primary Biliary Cirrhosis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

June 2012 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Alberta

Collaborators

Abbott, Gilead Sciences, Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Patients with primary biliary cirrhosis (PBC) develop progressive liver disease and often require liver transplantation. The cause of disease is unknown. It is thought to occur as a result of an infection in subjects that are more susceptible to disease than others. The investigators found evidence of retrovirus infection in patients with primary biliary cirrhosis. The investigators found that most patients with PBC have evidence of viral infection. Since then the investigators have conducted clinical studies using anti-viral therapy. The investigators found that PBC patients treated with combination anti-retrovirus therapy experienced significant reversal of the disease process. However, the changes were not substantial and the investigators are now looking for better antiviral regimens. Now the investigators have found a mouse model with a similar virus infection that develops a similar biliary disease. Importantly, the investigators found that antiviral therapy blocks the development of the disease in this mouse. The investigators have used this model to find safer and more effective antiviral treatments for patients with PBC. The investigators have now found out that a combination of highly active antiretroviral therapy with Truvada and Kaletra stops disease in the mouse and plan to use this combination to see if it works in patients with PBC.

Detailed Description

6 months therapy with blinded Kaletra and Truvada vs. 6 months therapy with blinded placebo followed by 6 months open label therapy with Kaletra and Truvada 18 month extension study with open label Kaletra and Truvada in patients completing 6 months of therapy with Kaletra and Truvada with biochemical endpoint

6. Conditions and Keywords

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

Primary Biliary Cirrhosis

Keywords

PBC

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

6 months therapy with blinded placebo followed by 6 months open label therapy with Kaletra and Truvada. Then there is an option for an 18 month follow-up study.

Arm Title

Truvada and Kaletra

Arm Type

Active Comparator

Arm Description

Patients will be take Truvada and Kaletra for 6 months with the option of open label for additional 18 months.

Intervention Type

Drug

Intervention Name(s)

Truvada and Kaletra

Other Intervention Name(s)

Truvada, Tenofovir, Emtricitabine, Kaletra, lopinavir, ritonavir

Intervention Description

one tablet of Truvada a day at standard dose of Tenofovir 300mg and Emtricitabine 200mg and four tablets of Kaletra once a day for a total dose of lopinavir 800mg and ritonavir 200mg for 6 months or less if adverse events occur

Primary Outcome Measure Information:

Title

Reduction of ALP to 1.67x ULN

Time Frame

The outcomes will be measured are from 12 to 24 weeks at the end of the study

Title

normalization of bilirubin.

Time Frame

The outcomes will be measured are from 12 to 24 weeks at the end of the study

Secondary Outcome Measure Information:

Title

Reduction of human betaretrovirus.

Time Frame