Study of Lanreotide to Treat Polycystic Kidney Disease

Summary

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys, in most patients leading to end stage renal disease. It is the most common hereditary renal disease with a prevalence of approximately 1 in 1,000 persons. The majority of patients also have progressive cyst formation in the liver, leading to pain, gastrointestinal discomfort and sometimes the need for liver transplantation. At present there is no proven therapeutic intervention to slow the rate of disease progression in human ADPKD. The development of renoprotective treatments that are well tolerated, is therefore of major importance. In this respect, somatostatin analogues are promising for especially polycystic liver disease, but also for the renal phenotype. However, the studies that have been performed thus far with these agents, were underpowered and of too short duration to reach a definitive conclusion on the potential reno- and hepatoprotective efficacy of somatostatin analogues. Therefore, the present study is designed as a randomised clinical trial with sufficient duration of follow-up to investigate whether the somatostatin analogue Lanreotide slows progression of polycystic kidney and liver disease in ADPKD-patients. To this end, 300 ADPKD patients, aged 18-60years, with an eGFR 30-60 ml/min/1.73 m2) will be randomized 1:1 to standard care or monthly subcutaneous lanreotide injections on top off standard care. These 300 subjects will go through 15 study visits in 3 years and 1 follow up visit. During these visits, questionnaires will be filled in, physical examinations will be performed, blood will be drawn and urine collected. After study completion, rate of renal function decline in lanreotide treated subjects will be compared to that of subject who received standard care.

Timeline

Start

2012-06

Primary completion

2017-08

Completion

2017-12

Publications

• Background Meijer E, Drenth JP, d'Agnolo H, Casteleijn NF, de Fijter JW, Gevers TJ, Kappert P, Peters DJ, Salih M, Soonawala D, Spithoven EM, Torres VE, Visser FW, Wetzels JF, Zietse R, Gansevoort RT; DIPAK Consortium. Rationale and design of the DIPAK 1 study: a randomized controlled clinical trial assessing the efficacy of lanreotide to Halt disease progression in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2014 Mar;63(3):446-55. doi: 10.1053/j.ajkd.2013.10.011. Epub 2013 Dec 15.
• Results Lantinga MA, D'Agnolo HM, Casteleijn NF, de Fijter JW, Meijer E, Messchendorp AL, Peters DJ, Salih M, Spithoven EM, Soonawala D, Visser FW, Wetzels JF, Zietse R, Drenth JP, Gansevoort RT; DIPAK Consortium. Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study. Drug Saf. 2017 Feb;40(2):153-167. doi: 10.1007/s40264-016-0486-x.
• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
• Aapkes SE, de Haas RJ, Bernts LHP, Blijdorp CJ, Dekker SEI, van Gastel MDA, Meijer E, Veldman A, Drenth JPH, Gansevoort RT; DIPAK consortium. Incident Gallstones During Somatostatin Analog Treatment are Associated with Acute Biliary Complications Especially After Discontinuation. Drugs R D. 2021 Jun;21(2):179-188. doi: 10.1007/s40268-021-00342-7. Epub 2021 Mar 29.
• van Aerts RMM, Kievit W, D'Agnolo HMA, Blijdorp CJ, Casteleijn NF, Dekker SEI, de Fijter JW, van Gastel M, Gevers TJ, van de Laarschot LFM, Lantinga MA, Losekoot M, Meijer E, Messchendorp AL, Neijenhuis MK, Pena MJ, Peters DJM, Salih M, Soonawala D, Spithoven EM, Visser FW, Wetzels JF, Zietse R, Gansevoort RT, Drenth JPH; DIPAK-1 Investigators. Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease. Gastroenterology. 2019 Aug;157(2):481-491.e7. doi: 10.1053/j.gastro.2019.04.018. Epub 2019 Apr 22.
• Meijer E, Visser FW, van Aerts RMM, Blijdorp CJ, Casteleijn NF, D'Agnolo HMA, Dekker SEI, Drenth JPH, de Fijter JW, van Gastel MDA, Gevers TJ, Lantinga MA, Losekoot M, Messchendorp AL, Neijenhuis MK, Pena MJ, Peters DJM, Salih M, Soonawala D, Spithoven EM, Wetzels JF, Zietse R, Gansevoort RT; DIPAK-1 Investigators. Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease: The DIPAK 1 Randomized Clinical Trial. JAMA. 2018 Nov 20;320(19):2010-2019. doi: 10.1001/jama.2018.15870.

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Indications