Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE): study protocol for a randomized controlled trial

This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed.This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume.ClinicalTrials.gov: NCT01157858Polycystic liver disease (PLD) is a condition that is arbitrarily defined as the presence of at least 20 liver cysts. The two genetic distinct disorders autosomal dominant polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD) are most frequently responsible for PLD[1]. In ADPKD there are polycystic kidneys which can be accompanied by liver cysts in up to 87% of the patients, depending on age and severity of renal impairment[2]. The phenotype of PLD can vary widely but in most advanced cases impairs quality of life by the mechanical complaints caused by the massively enlarged liver[3].Until recently, surgical procedures were the only treatment options to reduce polycystic liver volume. However, these invasive procedures are accompanied by relatively high morbidity and there is a small but detectable procedure related mortality[1]. In the last few years, medical treatment options have been explored as an alternative to invasive therapy. Somatostatin analogues by virtue of reducing cAMP in the cholangiocytes that line the cyst. The first signal of efficacy came from experimental studies in rodent PLD models where octreotide suppressed liver (-19%) and liver cyst (-40%) volumes[4]. This concept was further reinforced by several randomized clinical trials that