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

April 25, 2011
November 11, 2013
June 2012
September 2015   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01614405 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis
Randomized Controlled Pilot Study of Highly Active Anti-Retroviral Therapy for Patients With Primary Biliary Cirrhosis

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.

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

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Primary Biliary Cirrhosis
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
  • 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.
    Intervention: Drug: Truvada and Kaletra
  • 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.
    Intervention: Drug: Truvada and Kaletra
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
80
September 2015
September 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01614405
HAART Study
Yes
Andrew L. Mason, University of Alberta
University of Alberta
  • Abbott
  • Gilead Sciences
  • Canadian Institutes of Health Research (CIHR)
Principal Investigator: Andrew Mason University of Alberta
University of Alberta
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP