Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis (HAART)
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Primary Biliary Cirrhosis |
Drug: Truvada and Kaletra |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Randomized Controlled Pilot Study of Highly Active Anti-Retroviral Therapy for Patients With Primary Biliary Cirrhosis |
- 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 ] [ Designated as safety issue: Yes ]
- normalization of bilirubin. [ Time Frame: The outcomes will be measured are from 12 to 24 weeks at the end of the study ] [ Designated as safety issue: Yes ]
- Reduction of human betaretrovirus. [ Time Frame: The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study ] [ Designated as safety issue: No ]
- Symptoms with changes in PBC-40 [ Time Frame: The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study ] [ Designated as safety issue: No ]
- Changes in AMA and immunoglobulin levels [ Time Frame: The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study ] [ Designated as safety issue: No ]
- Biochemistry: GGT, AST and ALT [ Time Frame: The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study ] [ Designated as safety issue: Yes ]
- Histology in extension study [ Time Frame: The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 80 |
| Study Start Date: | June 2012 |
| Estimated Study Completion Date: | July 2015 |
| Estimated Primary Completion Date: | July 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Placebo
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.
|
Drug: Truvada and Kaletra
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
Other Names:
|
|
Active Comparator: Truvada and Kaletra
Patients will be take Truvada and Kaletra for 6 months with the option of open label for additional 18 months.
|
Drug: Truvada and Kaletra
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
Other Names:
|
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
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01614405
| Canada, Alberta | |
| University of Alberta | |
| Edmonton, Alberta, Canada, T6G 2B2 | |
| Principal Investigator: | Andrew Mason | University of Alberta |
More Information
Publications:
| Responsible Party: | Andrew L. Mason, Principal Investigator, University of Alberta |
| ClinicalTrials.gov Identifier: | NCT01614405 History of Changes |
| Other Study ID Numbers: | HAART Study |
| Study First Received: | April 25, 2011 |
| Last Updated: | December 1, 2014 |
| Health Authority: | Canada: Health Canada United States: Institutional Review Board France: Ministry of Health |
Keywords provided by University of Alberta:
|
PBC |
Additional relevant MeSH terms:
|
Liver Cirrhosis, Biliary Bile Duct Diseases Biliary Tract Diseases Cholestasis Cholestasis, Intrahepatic Digestive System Diseases Liver Cirrhosis Liver Diseases Lopinavir Anti-HIV Agents |
Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protease Inhibitors Therapeutic Uses |
ClinicalTrials.gov processed this record on March 03, 2015