Primary Biliary CirrhosisHAARTNCT01614405
Highly Active Antiretroviral Therapy for Patients With Primary Biliary Cirrhosis
A study testing TDF/FTC/LPV/r in people with Primary Biliary Cirrhosis, run by University of Alberta at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- TDF/FTC/LPV/r
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2012to Aug 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- TDF/FTC/LPV/r, Placebo
- Keywords
- PBC
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDF/FTC/LPV/rDrug
Also called Truvada, Tenofovir, Emtricitabine, 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
PlaceboDrug
Also called Truvada, Tenofovir, Emtricitabine, lopinavir
6 months therapy with blinded placebo followed by 6 months open label therapy with Kaletra and Truvada.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: TDF/FTC/LPV/r |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of ALP to 1.67x ULN
Measured: The outcomes will be measured are from 12 to 24 weeks at the end of the study
normalization of bilirubin.
Measured: The outcomes will be measured are from 12 to 24 weeks at the end of the study
Secondary outcomes (5)
Reduction of human betaretrovirus.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: The outcomes will be measured are from 12 to 24 weeks in RCT; and 6 monthly to 2 years for the extension study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2012 (estimated)
- Study startJun 2012
- Primary completionJul 2015
- Study completionAug 2015
Why it stopped: Protracted gastrointestinal symptoms were experienced by most patients who were subsequently found to be in the treatment arm on LPV/r. This observation resulted in cessation of enrolment and a decision not to continue the RCT
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Biliary CirrhosisStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott, Gilead Sciences, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Andrew Mason, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01614405
- Sponsor's protocol ID
- HAART Study
- Acronym
- HAART
- Status last verified
- Nov 2024
- First submitted
- 25 Apr 2011
- Last updated
- 21 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21195252
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Pilot Study of Highly Active Anti-Retroviral Therapy for Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT01614405
- Acronym / sponsor ID
- HAART / HAART Study
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- PBC
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Protracted gastrointestinal symptoms were experienced by most patients who were subsequently found to be in the treatment arm on LPV/r. This observation resulted in cessation of enrolment and a decision not to continue the RCT
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- Abbott, Gilead Sciences, Canadian Institutes of Health Research (CIHR)
- Study start
- Jun 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 7 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIdentical 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. |
| TDF/FTC/LPV/r | Active comparator | Drug: TDF/FTC/LPV/rTDF/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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDF/FTC/LPV/rAlso: Truvada, Tenofovir, Emtricitabine, Kaletraone 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 | Drug | TDF/FTC/LPV/r |
| PlaceboAlso: Truvada, Tenofovir, Emtricitabine, lopinavir6 months therapy with blinded placebo followed by 6 months open label therapy with Kaletra and Truvada. | Drug | Placebo |
Primary outcome
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
normalization of bilirubin.
Time frame: The outcomes will be measured are from 12 to 24 weeks at the end of the study
5 secondary outcomes
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
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
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
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
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
Results and safety
The study was stopped early (reason given: Protracted gastrointestinal symptoms were experienced by most patients who were subsequently found to be in the treatment arm on LPV/r. This observation resulted in cessation of enrolment and a decision not to continue the RCT). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2024.
- Background: PubMed 21195252Schembri 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Mason principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TDF/FTC/LPV/r in people with Primary Biliary Cirrhosis, run by University of Alberta at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Protracted gastrointestinal symptoms were experienced by most patients who were subsequently found to be in the treatment arm on LPV/r. This observation resulted in cessation of enrolment and a decision not to continue the RCT). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01614405, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2024.