Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease : the AGAINST-PLD study
Aapkes, S.E. (Department of Nephrology. University Medical Center Groningen. University of Groningen)
Bernts, L.H.P. (Department of Gastroenterology and Hepatology. Radboud University Medical Center)
van den Berg, A.P. (Department of Gastroenterology and Hepatology. University Medical Center Groningen. University of Groningen)
van den Berg, M. (Department of Obstetrics and Gynecology. University Medical Center Groningen. University of Groningen)
Blokzijl, H. (Department of Gastroenterology and Hepatology. University Medical Center Groningen. University of Groningen)
Cantineau, Astrid E P (Department of Obstetrics and Gynecology. University Medical Center Groningen. University of Groningen)
van Gastel, M.D.A. (Department of Nephrology. University Medical Center Groningen. University of Groningen)
de Haas, R.J. (Department of Radiology. University Medical Center Groningen. University of Groningen)
Kappert, P. (Department of Radiology. University Medical Center Groningen. University of Groningen)
Müller, R.U. (Department II of Internal Medicine and Center for Molecular Medicine Cologne. Faculty of Medicine. University Hospital Cologne. University of Cologne)
Nevens, F. (Department of Gastroenterology and Hepatology. Universiteitsziekenhuis Leuven)
Torra Balcells, Roser (Institut d'Investigació Biomèdica Sant Pau)
Visser, A. (Department of Applied Health Sciences. University Medical Center Groningen. University of Groningen)
Drenth, J.P.H. (Department of Gastroenterology and Hepatology. Radboud University Medical Center)
Gansevoort, R.T. (Department of Nephrology. University Medical Center Groningen. University of Groningen)

Date:	2022
Abstract:	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. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www. clinicaltrialsregister. eu/ctr-search/search?query=2020-005949-16.
Note:	Altres ajuts: Dutch Government (ZonMW grant 10140261910001); Abbvie (SA-003047 (ACA-NETH-20-01)).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Polycystic liver disease ; GnRHa ; Estrogen
Published in:	BMC Gastroenterology, Vol. 22 Núm. 1 (december 2022) , p. 82, ISSN 1471-230X

DOI: 10.1186/s12876-022-02142-y
PMID: 35216547

11 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
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