Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study
Por:
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
Publicada:
25 feb 2022
Resumen:
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.
Filiaciones:
Aapkes, SE:
Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands
Bernts, LHP:
Radboud Univ Nijmegen Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands
van den Berg, AP:
Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands
van den Berg, M:
Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands
Blokzijl, H:
Univ Groningen, Univ Med Ctr Groningen, Dept Gastroenterol & Hepatol, Groningen, Netherlands
Cantineau, AEP:
Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands
van Gastel, MDA:
Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands
de Haas, RJ:
Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands
Kappert, P:
Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands
Muller, RU:
Univ Cologne, Univ Hosp Cologne, Fac Med, Dept Internal Med 2, Kerpener Str 62, D-50937 Kerpener Strae, Germany
Univ Cologne, Univ Hosp Cologne, Fac Med, Ctr Mol Med Cologne, Kerpener Str 62, D-50937 Kerpener Strae, Germany
Nevens, F:
Univ Ziekenhuis Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium
Torra, R:
Fundacio Puigvert, Dept Nephrol, Barcelona, Spain
Visser, A:
Univ Groningen, Univ Med Ctr Groningen, Dept Appl Hlth Sci, Groningen, Netherlands
Drenth, JPH:
Radboud Univ Nijmegen Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands
Gansevoort, RT:
Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands
Green Published, gold
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