Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Tom J G Gevers, Melissa Chrispijn, Jack F M Wetzels, Joost P H Drenth, Tom J G Gevers, Melissa Chrispijn, Jack F M Wetzels, Joost P H Drenth

Abstract

Background: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD). The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial.

Methods/design: This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, α1-microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23) biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed.

Discussion: We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response.

Trial registration number: Clinical trials.gov NCT01354405.

Figures

Figure 1
Figure 1
RESOLVE trial profile. ADPDK subjects are screened for eligibility, and 43 ADPKD patients with symptomatic polycystic liver disease and eGFR > 30 ml/min (MDRD formula) will be included. At day 1, all patients undergo CT volumetry of liver and kidneys. Patients without polycystic type II or III livers, as determined with CT volumetry, will be excluded from the study. Interval visits are scheduled 4 and 12 weeks after start of treatment. After 24 weeks of treatment with lanreotide (6 injections), another CT will be performed to evaluate the change in liver and kidney volume.

References

    1. Dalgaard OZ. Bilateral polycystic disease of the kidneys; a follow-up of two hundred and eighty-four patients and their families. Acta Med Scand Suppl. 1957;328:1–255.
    1. Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369:1287–301. doi: 10.1016/S0140-6736(07)60601-1.
    1. Gulick JJM, Gevers TJ, van Keimpema L, Drenth JP. Hepatic and renal manifestations in autosomal dominant polycystic kidney disease: dichotomy of a spectrum. Neth J Med. in press .
    1. Gabow PA, Johnson AM, Kaehny WD, Manco-Johnson ML, Duley IT, Everson GT. Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. Hepatology. 1990;11:1033–7. doi: 10.1002/hep.1840110619.
    1. Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr. et al.Volume progression in polycystic kidney disease. N Engl J Med. 2006;354:2122–30. doi: 10.1056/NEJMoa054341.
    1. Caroli A, Antiga L, Cafaro M, Fasolini G, Remuzzi A, Remuzzi G. et al.Reducing polycystic liver volume in ADPKD: effects of somatostatin analogue octreotide. Clin J Am Soc Nephrol. 2010;5:783–9. doi: 10.2215/CJN.05380709.
    1. Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X. et al.Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol. 2010;21:1052–61. doi: 10.1681/ASN.2009121291.
    1. van Keimpema L, Nevens F, Vanslembrouck R, van Oijen MG, Hoffmann AL, Dekker HM. et al.Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. Gastroenterology. 2009;137:1661–8. doi: 10.1053/j.gastro.2009.07.052.
    1. Everson GT, Taylor MR, Doctor RB. Polycystic disease of the liver. Hepatology. 2004;40:774–82.
    1. Fick GM, Gabow PA. Natural history of autosomal dominant polycystic kidney disease. Annu Rev Med. 1994;45:23–9. doi: 10.1146/annurev.med.45.1.23.
    1. Drenth JP, Chrispijn M, Nagorney DM, Kamath PS, Torres VE. Medical and surgical treatment options for polycystic liver disease. Hepatology. 2010;52:2223–30. doi: 10.1002/hep.24036.
    1. Gevers TJ, Drenth JP. Somatostatin analogues for treatment of polycystic liver disease. Curr Opin Gastroenterol. 2011;27:294–300. doi: 10.1097/MOG.0b013e328343433f.
    1. van Keimpema L, de Man RA, Drenth JP. Somatostatin analogues reduce liver volume in polycystic liver disease. Gut. 2008;57:1338–9. doi: 10.1136/gut.2008.155721.
    1. van Keimpema L, Drenth JP. Effect of octreotide on polycystic liver volume. Liver Int. 2010;30:633–4. doi: 10.1111/j.1478-3231.2009.02123.x.
    1. Caroli A, Antiga L, Conti S, Sonzogni A, Fasolini G, Ondei P. et al.Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients. Am J Pathol. 2011;179:619–27. doi: 10.1016/j.ajpath.2011.04.036.
    1. Meijer E, Boertien WE, Nauta FL, Bakker SJ, van Oeveren W, Rook M. et al.Association of urinary biomarkers with disease severity in patients with autosomal dominant polycystic kidney disease: a cross-sectional analysis. Am J Kidney Dis. 2010;56:883–95. doi: 10.1053/j.ajkd.2010.06.023.
    1. Pavik I, Jaeger P, Kistler AD, Poster D, Krauer F, Cavelti-Weder C. et al.Patients with autosomal dominant polycystic kidney disease have elevated fibroblast growth factor 23 levels and a renal leak of phosphate. Kidney Int. 2011;79:234–40. doi: 10.1038/ki.2010.375.
    1. Gigot JF, Jadoul P, Que F, Van Beers BE, Etienne J, Horsmans Y. et al.Adult polycystic liver disease: is fenestration the most adequate operation for long-term management? Ann Surg. 1997;225:286–94. doi: 10.1097/00000658-199703000-00008.
    1. Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994;343:824–7. doi: 10.1016/S0140-6736(94)92026-5.
    1. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70.
    1. Antiga L, Piccinelli M, Fasolini G, Ene-Iordache B, Ondei P, Bruno S. et al.Computed tomography evaluation of autosomal dominant polycystic kidney disease progression: a progress report. Clin J Am Soc Nephrol. 2006;1:754–60. doi: 10.2215/CJN.02251205.
    1. 2011. Ref Type: Internet communication.
    1. Bovenschen HJ, Janssen MJ, van Oijen MG, Laheij RJ, van Rossum LG, Jansen JB. Evaluation of a gastrointestinal symptoms questionnaire. Dig Dis Sci. 2006;51:1509–15. doi: 10.1007/s10620-006-9120-6.
    1. Otsu N. A threshold selection method from gray-level histogram. IEEE Trans Syst Man Cybern. 1979;9:5.
    1. Ruggenenti P, Remuzzi A, Ondei P, Fasolini G, Antiga L, Ene-Iordache B. et al.Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease. Kidney Int. 2005;68:206–16. doi: 10.1111/j.1523-1755.2005.00395.x.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다