Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study

Background: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The...

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Autores: Aapkes, SE, Bernts, LHP, van den Berg, AP, van den Berg, M, Blokzijl, H, Cantineau, AEP, van Gastel, MDA, de Haas, RJ, Kappert, P, Muller, RU, Nevens, F, Torra, R, Visser, A, Drenth, JPH, Gansevoort, RT
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p8121
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8121
https://ddd.uab.cat/record/275181
Access Level:acceso abierto
Palabra clave:Polycystic liver disease
GnRHa
Estrogen
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spelling Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD studyAapkes, SEBernts, LHPvan den Berg, APvan den Berg, MBlokzijl, HCantineau, AEPvan Gastel, MDAde Haas, RJKappert, PMuller, RUNevens, FTorra, RVisser, ADrenth, JPHGansevoort, RTPolycystic liver diseaseGnRHaEstrogenBackground: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. Methods: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). Discussion: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD.BMC2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8121https://ddd.uab.cat/record/275181BMC GASTROENTEROLOGYISSN: 1471230Xreponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p81212026-06-14T12:41:47Z
dc.title.none.fl_str_mv Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
title Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
spellingShingle Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
Aapkes, SE
Polycystic liver disease
GnRHa
Estrogen
title_short Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
title_full Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
title_fullStr Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
title_full_unstemmed Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
title_sort Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
dc.creator.none.fl_str_mv Aapkes, SE
Bernts, LHP
van den Berg, AP
van den Berg, M
Blokzijl, H
Cantineau, AEP
van Gastel, MDA
de Haas, RJ
Kappert, P
Muller, RU
Nevens, F
Torra, R
Visser, A
Drenth, JPH
Gansevoort, RT
author Aapkes, SE
author_facet Aapkes, SE
Bernts, LHP
van den Berg, AP
van den Berg, M
Blokzijl, H
Cantineau, AEP
van Gastel, MDA
de Haas, RJ
Kappert, P
Muller, RU
Nevens, F
Torra, R
Visser, A
Drenth, JPH
Gansevoort, RT
author_role author
author2 Bernts, LHP
van den Berg, AP
van den Berg, M
Blokzijl, H
Cantineau, AEP
van Gastel, MDA
de Haas, RJ
Kappert, P
Muller, RU
Nevens, F
Torra, R
Visser, A
Drenth, JPH
Gansevoort, RT
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Polycystic liver disease
GnRHa
Estrogen
topic Polycystic liver disease
GnRHa
Estrogen
description Background: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. Methods: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). Discussion: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8121
https://ddd.uab.cat/record/275181
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8121
https://ddd.uab.cat/record/275181
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv BMC GASTROENTEROLOGY
ISSN: 1471230X
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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