NCT02768545

Brief Summary

NPC1L1 is 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. 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. To prove this hypothesis the investigators propose to assess the effect of ezetimibe treatment in HCV infected individuals undergoing liver transplantation to avoid or delay HCV infection. For this purpose, the investigators propose to administrate ezetimibe 10 mg/d for 12 weeks to 12 patients with chronic hepatitis C infection listed for a liver transplantation.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
12

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jun 2013

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2013

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

May 8, 2016

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 11, 2016

Completed
21 days until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

May 11, 2016

Status Verified

May 1, 2016

Enrollment Period

2.9 years

First QC Date

May 8, 2016

Last Update Submit

May 10, 2016

Conditions

Hepatitis C

Keywords

Hepatitis CEzetimibeCholesterolEnterohepatic CirculationBileFeces

Outcome Measures

Primary Outcomes (1)

  • Controlled viral load

    Proportion of patients with HCV viral load lower than pre-transplant viral load measured at 4 weeks after liver transplant.

    4 weeks after liver transplantation

Secondary Outcomes (1)

  • Sustained virologic response

    12 weeks

Study Arms (1)

Liver transplant candidates

EXPERIMENTAL

Ezetimibe in a dose of 10 mg/d for 12 weeks.

Drug: Ezetimibe

Interventions

EzetimibeDRUG

Ezetimibe 10 mg per day before and after transplant

Liver transplant candidates

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Chronic hepatitis C defined as detectable HCV RNA for more than 6 months.
  • Age \> 18 years old.
  • No current HCV antiviral treatment.
  • No medications for dyslipidemia in the preceding 2 months.
  • Listed in the national waiting list for liver transplant with an estimated time to transplantation of 3 months or less, either for complications of cirrhosis or for hepatocellular carcinoma.
  • No abdominal surgery that could alter biliary or intestinal anatomy.
  • HCV RNA level \> 10.000 IU/mL.
  • No evidence of sitosterolemia.
  • Negative pregnancy test in urine (for females).
  • Signed informed consent document.

You may not qualify if:

  • Hepatitis B or HIV co-infection.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Departamento de Gastroenterología, Pontificia Universidad Católica de Chile

Santiago, RM, 833-0024, Chile

RECRUITING

Related Publications (9)

  • Agnello V, Abel G, Elfahal M, Knight GB, Zhang QX. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12766-71. doi: 10.1073/pnas.96.22.12766.

    PMID: 10535997BACKGROUND

  • Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem. 1974 Apr;20(4):470-5. No abstract available.

    PMID: 4818200BACKGROUND

  • Beld M, Sentjens R, Rebers S, Weel J, Wertheim-van Dillen P, Sol C, Boom R. Detection and quantitation of hepatitis C virus RNA in feces of chronically infected individuals. J Clin Microbiol. 2000 Sep;38(9):3442-4. doi: 10.1128/JCM.38.9.3442-3444.2000.

    PMID: 10970398BACKGROUND

  • Ge L, Wang J, Qi W, Miao HH, Cao J, Qu YX, Li BL, Song BL. The cholesterol absorption inhibitor ezetimibe acts by blocking the sterol-induced internalization of NPC1L1. Cell Metab. 2008 Jun;7(6):508-19. doi: 10.1016/j.cmet.2008.04.001.

    PMID: 18522832BACKGROUND

  • Haruna Y, Kanda T, Honda M, Takao T, Hayashi N. Detection of hepatitis C virus in the bile and bile duct epithelial cells of hepatitis C virus-infected patients. Hepatology. 2001 Apr;33(4):977-80. doi: 10.1053/jhep.2001.23435.

    PMID: 11283863BACKGROUND

  • Jia L, Betters JL, Yu L. Niemann-pick C1-like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu Rev Physiol. 2011;73:239-59. doi: 10.1146/annurev-physiol-012110-142233.

    PMID: 20809793BACKGROUND

  • Nielsen SU, Bassendine MF, Burt AD, Martin C, Pumeechockchai W, Toms GL. Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J Virol. 2006 Mar;80(5):2418-28. doi: 10.1128/JVI.80.5.2418-2428.2006.

    PMID: 16474148BACKGROUND

  • Sainz B Jr, Barretto N, Martin DN, Hiraga N, Imamura M, Hussain S, Marsh KA, Yu X, Chayama K, Alrefai WA, Uprichard SL. Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nat Med. 2012 Jan 8;18(2):281-5. doi: 10.1038/nm.2581.

    PMID: 22231557BACKGROUND

  • Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson LM, Yu L. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest. 2007 Jul;117(7):1968-78. doi: 10.1172/JCI30060.

    PMID: 17571164BACKGROUND

MeSH Terms

Conditions

Hepatitis C

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitisLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

AzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Alejandro Soza, MD

    Pontificia Universidad Catolica de Chile

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Alejandro Soza, MD

CONTACT

56-22-345-3820asoza@med.puc.cl

Hugo Monrroy, MD

CONTACT

56-22-345-3820hmonrroy@med.puc.cl

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

May 8, 2016

First Posted

May 11, 2016

Study Start

June 1, 2013

Primary Completion

May 1, 2016

Study Completion

June 1, 2016

Last Updated

May 11, 2016

Record last verified: 2016-05

Data Sharing

IPD Sharing
Will not share

Locations

CL(1)