ADPKD Clinical Trial
Official title:
Rapamycin in Advanced Polycystic Kidney Disease Pilot Study
The purpose of this study is to evaluate the safety of a daily single oral dose of sirolimus in patients with advanced autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of renal cystic
diseases, affecting all ethnic groups with an incidence of 1 in 400 to 1.000. In Austria an
estimated 8.000 to 21.000 people, and an estimated 670.000 to 1.675.000 people worldwide are
affected by ADPKD, although statements of up to 6.000.000 affected individuals have been
made. ADPKD is responsible for 5 to 10 percent of patients on chronic hemodialysis.
Individuals with ADPKD usually present in the 3rd to 4th decade of life, progressing to
end-stage renal disease within 5 to 10 years after the onset of renal insufficiency. Usually
renal replacement therapy, either by chronic dialysis or renal transplantation, becomes
necessary. Currently there is no treatment for ADPKD other than blood pressure control and
supportive care.
Thus, novel therapies for ADPKD are of great importance.
The formation of cysts in ADPKD follows a mutation located within either the polycystic
kidney disease 1 or -2 gene on chromosomes 16 and 4, which are coding for polycystin 1 (PC1)
and -2 (PC2), respectively. PC1 and PC2 are members of the polycystin family of integral
membrane proteins. PC1 acts as a G-protein coupled receptor and is suggested to mediate
cell-cell and cell-matrix interactions. PC2 acts as a nonselective cation channel and is
supposed to act in ion exchange mechanisms. Among other pathways PC1 and 2 are functioning
via a mammalian target of rapamycin (mTOR) pathway, which is essential in protein
translation, cell proliferation and -growth. Inhibition of the mTOR-pathway has reduced
kidney enlargement in rodent polycystic kidney disease models and has shown to reduce the
volume of cysts in human polycystic kidney- and polycystic liver disease. Thus, we
hypothesize that the mTOR inhibitor sirolimus, an immunosuppressant drug with strong
anti-proliferative effects, will delay the progression of renal insufficiency in patients
with ADPKD in advanced stages of the disease.
Before conducting a large multicenter randomized controlled trial in this population we will
demonstrate that therapy with mTOR-I does not accelerate the decline in renal function (as
natural course of the disease), as well as mTOR-I does not aggravate prevalent-, or cause
new onset of proteinuria, as expressed by the protein/creatinine ratio, in patients with
ADPKD and an eGFR between 20 and 40 mL/min per 1.73sqm, compared to a historic cohort of
patients with ADPKD and an eGFR between 20 and 40 mL/min per 1.73sqm, treated at the
Department of Medicine III, Division of Nephrology and Dialysis, Medical University Vienna.
;
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04310319 -
Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt
|
N/A | |
Completed |
NCT02776241 -
Effect of Water Intake and Water Restriction on Total Kidney Volume in Autosomal Dominant Polycystic Kidney Disease
|
N/A | |
Terminated |
NCT04152837 -
Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease
|
Phase 3 | |
Completed |
NCT03717883 -
ADPKD Alterations in Hepatic Transporter Function
|
||
Recruiting |
NCT05014178 -
Kidney Sodium Functional Imaging
|
||
Recruiting |
NCT05521191 -
A Study of RGLS8429 in Patients With Autosomal Dominant Polycystic Kidney Disease
|
Phase 1 | |
Terminated |
NCT04064346 -
Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease
|
Phase 3 | |
Completed |
NCT03203642 -
Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD
|
Phase 2 | |
Recruiting |
NCT04338048 -
Autosomal Dominant Polycystic Kidney Disease (ADPKD) Study
|
||
Not yet recruiting |
NCT06100133 -
Treat Autosomal Dominant Polycystic Kidney Disease With Oral Ketone Ester?
|
Phase 2 | |
Terminated |
NCT03918447 -
A Trial of Bardoxolone Methyl in Patients With ADPKD - FALCON
|
Phase 3 | |
Recruiting |
NCT06416761 -
Genetics in the Progression of Nephropathies
|
||
Not yet recruiting |
NCT05373264 -
HYDROchlorothiazide to PROTECT Polycystic Kidney Disease Patients and Improve Their Quality of Life
|
Phase 3 | |
Recruiting |
NCT06085807 -
Genetic Testing in Autosomal Dominant Polycystic Kidney Disease
|
||
Completed |
NCT01853553 -
Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
|
Phase 3 | |
Completed |
NCT04472624 -
Short Term Induction of Ketosis in PKD
|
N/A | |
Not yet recruiting |
NCT03764605 -
Metformin vs Tolvaptan for Treatment of Autosomal Dominant Polycystic Kidney Disease
|
Phase 3 | |
Completed |
NCT04680780 -
Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
|
N/A | |
Completed |
NCT02161068 -
Clinical Care of Autosomal Polycystic Kidney Disease: Retrospective Analysis and Prospective PKD Genotyping
|
||
Active, not recruiting |
NCT03273413 -
Statin Therapy in Patients With Early Stage ADPKD
|
Phase 4 |