Combination Antiretroviral Therapy (cART) for PBC
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|ClinicalTrials.gov Identifier: NCT03954327|
Recruitment Status : Not yet recruiting
First Posted : May 17, 2019
Last Update Posted : May 21, 2019
|Condition or disease||Intervention/treatment||Phase|
|Primary Biliary Cholangitis||Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) Drug: Raltegravir Drug: Placebo Oral Capsule [CEBOCAP]||Phase 2|
Greater than 10% difference in mean percentage of alkaline phosphatase (ALP) reduction in cART vs. placebo at 6 and 12 months.
- Serum biochemistries bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) will be studied as continuous variables.
- Composite endpoint used for the POISE study [A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis]: (i) reduction of ALP to < 1.67 upper limit of normal, (ii) normalization of bilirubin within upper limit of normal (ULN) and (iii) reduction of ALP by > 15% at 6 and 12 months.
- Symptomatic evaluation performed using the PBC-40 to assess five symptom domains relating to fatigue, itch, cognitive symptoms, social and emotional symptoms, and other symptoms.
- Histological change in grade and stage of PBC using the Nakanuma scoring system for a subgroup of patients undergoing liver biopsy [liver biopsy not compulsory for study].
- Serial human betaretrovirus measurement in peripheral blood and cellular immune response to viral peptides.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Randomized Controlled Trail (RCT) of Emtricitabine, Tenofovir Disoproxil and Raltegravir for Patients With Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid (UDCA)|
|Estimated Study Start Date :||May 2019|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2023|
|Experimental: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir||
Drug: Emtricitabine (FTC)/Tenofovir Disoproxil (TDF)
Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day
Raltegravir (RTF) 600 mg two tablets by mouth once per day
|Placebo Comparator: Placebo||
Drug: Placebo Oral Capsule [CEBOCAP]
Two capsules identical to Raltegravir and one capsule identical to Truavda with no active ingredients by mouth once per day
- Change in alkaline phosphatase levels [ Time Frame: 12 months ]Mean changes in alkaline phosphatase levels after 12 months treatment with combination antiretroviral therapy or placebo.
- Serial changes in alkaline phosphatase [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy] ]Serial changes in alkaline phosphatase levels with combination antiretroviral therapy or placebo.
- Serial changes in ALT [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy] ]Serial changes in ALT levels with combination antiretroviral therapy or placebo.
- Serial changes in bilirubin [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy] ]Serial changes in bilirubin levels with combination antiretroviral therapy or placebo.
- Achievement of the composite biochemistry endpoint [ Time Frame: 6 and 12 months ](i) reduction of ALP to < 1.67 upper limit of normal, (ii) normalization of bilirubin within ULN and (iii) reduction of ALP by > 15%
- Human Betaretrovirus load in peripheral blood [ Time Frame: Evaluation baseline, 3 months, 6 months and end of RCT; then 3 months, 6 monthly to end of open label therapy ]Quantification of Human Betaretrovirus DNA or RNA levels in peripheral blood measured by Quantigene or polymerase chain reaction with therapy or placebo.
- Interferon gamma release to Human Betaretrovirus peptide stimulation [ Time Frame: Evaluation at baseline, 6 months and end of RCT; then 6 monthly to end of open label therapy ]Concentration of interferon gamma released from peripheral blood mononuclear cells stimulated by Human Betaretrovirus peptides in vitro in response to treatment or placebo.
- Liver histology [ Time Frame: Pretreatment biopsy and 24 month biopsy after initiation of study therapy ]Liver histology will be measured in a scale for staging and grading disease using the Nakanumuna scoring system. Scores for fibrosis, bile duct loss, and chronic cholestasis will be combined for staging: stage 1, total score of 0; stage 2, score 1-3; stage 3, score 4-6; and stage 4, score 7-9. Cholangitis activity and hepatitis activity will be graded as 0-3, respectively.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03954327
|Contact: Andrew Mason, MDfirstname.lastname@example.org|
|Contact: Breanne Stewart, RNemail@example.com|
|University of Alberta||Not yet recruiting|
|Edmonton, Alberta, Canada, T6G 2R3|
|Contact: Andrew Mason, MD 780-492-8172 firstname.lastname@example.org|
|Contact: Breanne Stewart, RN 780-9748606 email@example.com|
|Sub-Investigator: Aldo Montano Loza, MD|
|Sub-Investigator: Schokrollah Elahi, PhD|
|Canada, British Columbia|
|University of British Columbia||Not yet recruiting|
|Vancouver, British Columbia, Canada, V6Z 2C5|
|Contact: Eric Yoshida, MD firstname.lastname@example.org|
|Sub-Investigator: Vladimir Marquez, MD|
|Sub-Investigator: Hin Hin Ko, MD|
|University of Toronto||Not yet recruiting|
|Toronto, Ontario, Canada, M5S 1A1|
|Contact: Aliya Gulamhusein, MD Aliya.Gulamhusein@uhn.ca|
|Montréal, Quebec, Canada|
|University of Montreal||Not yet recruiting|
|Montréal, Quebec, Canada|
|Contact: Catherine Vincent, MD email@example.com|
|Principal Investigator:||Andrew Mason, MD||University of Alberta|