Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis

NCT01614405 | Terminated DMC

• 1 other identifier: HAART Study
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Biliary Cirrhosis

Keywords

PBC

Outcome Measures

Primary Outcomes (2)

• Reduction of ALP to 1.67x ULN

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

• normalization of bilirubin.

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

Secondary Outcomes (5)

• Reduction of human betaretrovirus.

  The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study

• Symptoms with changes in PBC-40

  The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study

• Changes in AMA and immunoglobulin levels

  The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study

• Biochemistry: GGT, AST and ALT

  The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study

• Histology in extension study

  The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Identical Placebo Tablets. Duration: 6 months therapy with blinded placebo followed by 6 months open label therapy (Truvada and Kaletra). Following, there is an option for an 18-month extension study.

Drug: Placebo

TDF/FTC/LPV/r

ACTIVE COMPARATOR

TDF/FTC/LPV/r 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. Duration: 6 months of therapy with the option of open label for additional 18-month extension study.

Drug: TDF/FTC/LPV/r

Interventions

TDF/FTC/LPV/r DRUG

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

Also known as: Truvada, Tenofovir, Emtricitabine, Kaletra, lopinavir, ritonavir

TDF/FTC/LPV/r

Placebo DRUG

6 months therapy with blinded placebo followed by 6 months open label therapy with Kaletra and Truvada.

Also known as: Truvada, Tenofovir, Emtricitabine, lopinavir, ritonavir

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alberta: lead
• Abbott: collaborator
• Gilead Sciences: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2B2, Canada

Location

Related Publications (1)

• Schembri G, Schober P. Killing two birds with one stone. Lancet. 2011 Jan 1;377(9759):96. doi: 10.1016/S0140-6736(10)61343-8. No abstract available.

  PMID: 21195252 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; Emtricitabine; lopinavir-ritonavir drug combination; Lopinavir; Ritonavir

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyrimidinones; Thiazoles; Sulfur Compounds; Azoles

Study Officials

• Andrew Mason

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2011
• First Posted: June 7, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 21, 2024

Record last verified: 2024-11

Locations

CA (1)