Study of Ezetimibe for Chronic Hepatitis C Virus (HCV) Infection in Liver Transplant Candidates (EZE-2) (EZE-2)
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|ClinicalTrials.gov Identifier: NCT02768545|
Recruitment Status : Unknown
Verified May 2016 by Alejandro Soza, MD, Pontificia Universidad Catolica de Chile.
Recruitment status was: Recruiting
First Posted : May 11, 2016
Last Update Posted : May 11, 2016
|Condition or disease||Intervention/treatment||Phase|
|Hepatitis C||Drug: Ezetimibe||Phase 4|
Infection by hepatitis C virus (HCV) affects more than 170 million people in the World and 80.000 in Chile. It causes more deaths than HIV infection in the US and is a leading cause of liver transplantation in Chile. Even though treatments are evolving with new direct antiviral agents (DAAs) with increasing response rates, there are several issues with these new approaches, including toxicity, need for using interferon and ribavirin, complex algorithms of treatment, high cost, limited effectivity in certain groups (liver transplant patients) and drug interactions. Treatments targeted at host factors required for the viral cycle are becoming increasingly explored as an alternative or complement to DAAs. HCV has a very intimate connection with host lipidic pathways, altering the lipid profile, circulating bound to lipoproteins and using cholesterol receptors and intracellular mechanisms of fat metabolism. It has been recently described that NPC1L1 (Niemann-Pick C1-like 1), the intestinal receptor of cholesterol, serves as an entry factor for HCV. Interestingly, this receptor is not only expressed in the enterocytes (absorbing both endogenous and dietary cholesterol), but also in the canalicular membrane of the hepatocyte, where it functions absorbing cholesterol secreted into the canalicular lumen. NPC1L1 is, therefore, a key transporter in the enterohepatic cycle of cholesterol. Initial in-vitro and in-vivo data show that blocking this receptor with ezetimibe results in delaying infection in these models. Moreover, it has reported the case of a patient that after 3 unsuccessful treatment attempts, cleared HCV RNA with ezetimibe treatment, being the first report of the effect of ezetimibe in humans. In view of these observations, the investigators hypothesize that HCV has an enterohepatic cycle, being secreted in bile and reabsorbed either in the canalicular membrane or in the intestine by association with NPC1L1, following a path similar to the cycle of cholesterol in humans.
This possibility is further supported by the observation that HCV RNA has been detected in bile and feces of infected humans. To prove this hypothesis, the investigators propose to assess the effect of ezetimibe treatment in HCV-infected individuals. Ezetimibe is an approved and generally safe drug used for the management of hypercholesterolemia. HCV RNA and core antigen in plasma and feces will be assessed. An increase in bile or fecal HCV load after antagonizing NPC1L1 with ezetimibe will support the notion that HCV is reabsorbed in the canalicular membrane or at the intestinal level. The second part of the proposed study will be conducted in 12 patients who have chronic hepatitis C and are listed for a liver transplantation. Graft reinfection after liver transplant is universal. Here the investigators anticipate that the use of ezetimibe will directly impact on the reinfection time of the graft, by delaying or even preventing liver reinfection in some patients. Should this study be successful it will for sure have enormous implications for the design of novel management strategies for liver transplant patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Ezetimibe for Chronic Hepatitis C Virus (HCV) Infection in Liver Transplant Candidates (EZE-2)|
|Study Start Date :||June 2013|
|Actual Primary Completion Date :||May 2016|
|Estimated Study Completion Date :||June 2016|
Experimental: Liver transplant candidates
Ezetimibe in a dose of 10 mg/d for 12 weeks.
Ezetimibe 10 mg per day before and after transplant
- Controlled viral load [ Time Frame: 4 weeks after liver transplantation ]Proportion of patients with HCV viral load lower than pre-transplant viral load measured at 4 weeks after liver transplant.
- Sustained virologic response [ Time Frame: 12 weeks ]Percentage of participants with HCV viral load < 25 IU/mL after 12 weeks of completing treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02768545
|Contact: Alejandro Soza, MDemail@example.com|
|Contact: Hugo Monrroy, MDfirstname.lastname@example.org|
|Departamento de Gastroenterología, Pontificia Universidad Católica de Chile||Recruiting|
|Santiago, RM, Chile, 833-0024|
|Contact: Alejandro Soza, MD 56-22-6397780 email@example.com|
|Contact: Hugo Monrroy, MD 56-22-6397780 firstname.lastname@example.org|
|Principal Investigator:||Alejandro Soza, MD||Pontificia Universidad Catolica de Chile|