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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Abbott
Gilead Sciences
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Andrew L. Mason, University of Alberta
ClinicalTrials.gov Identifier:
NCT01614405
First received: April 25, 2011
Last updated: November 11, 2013
Last verified: November 2013
  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

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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: September 2015
Estimated Primary Completion Date: September 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:
  • Truvada
  • Tenofovir
  • Emtricitabine
  • Kaletra
  • lopinavir
  • ritonavir
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:
  • Truvada
  • Tenofovir
  • Emtricitabine
  • Kaletra
  • lopinavir
  • ritonavir

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
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Subjects with baseline AST or ALT > 5 x ULN.
  2. 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.
  3. 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.
  4. 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.
  5. An ultrasound showing a hepatic mass consistent with hepatocellular carcinoma within the last year in patients with cirrhosis.
  6. Previous allergic reaction to study medications.
  7. 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

  8. Pregnancy or breast-feeding a child. Young sexually active patients not using contraception
  9. Young sexually active patients not using contraception.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01614405

Locations
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2B2
Sponsors and Collaborators
University of Alberta
Abbott
Gilead Sciences
Canadian Institutes of Health Research (CIHR)
Investigators
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: November 11, 2013
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
Liver Cirrhosis
Fibrosis
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Ritonavir
Lopinavir
Tenofovir
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014