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Sirolimus Treatment in Patients With Autosomal Dominant Polycystic Kidney Disease: Renal Efficacy and Safety

NCT00491517 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2013-04-24

No results posted yet for this study

Summary

Autosomal-Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary renal disease, characterized by the progressive development of fluid-filled cysts in the kidney leading to progressive loss of renal function and eventually to renal failure. It is responsible for 8% to 10% of the cases of end stage renal disease (ESRD) in Western countries. ADPKD progression is largely dependent on the development and growth of the cysts and secondary disruption of the normal tissue. Renoprotective interventions in ADPKD - in addition to achieve maximal reduction of arterial blood pressure and proteinuria and to limit the effects of additional potential promoters of disease progression such as dyslipidemia, chronic hyperglycemia or smoking - should also be specifically aimed to correct the dysregulation of epithelial cell growth, secretion, and matrix interactions characteristic of the disease. Genetically in the ADPKD three different genes are implicated (PKD1 85% of the cases, PKD2 15% and probably PDK3 not yet identified). PKD1 gene encodes a protein named polycystin-1 (PC1). Defect in PC1 lead to aberrant activation of the enzyme mTOR in the epithelial cells of the renal tubules which eventually leads to abnormal proliferation of these cells and cysts generation.

Sirolimus (Rapamycin) is an immunosuppressant mostly used for the management of kidney transplant recipients. This drug by very specifically and effectively inhibiting mTOR, exerts antiproliferative and growth inhibiting effects and could be extremely important for the inhibition of cyst progression in ADPKD. Animal models of ADPKD have shown that short-term treatment with sirolimus resulted in dramatic reduction of kidney size, prevented the loss of kidney function, and lowered cyst volume density. Similarly, retrospective observations from kidney transplant recipients have documented that sirolimus treatment reduced kidney volumes by 25%, whereas there was no effect in patients not given the drug.

Overall, these findings provide the basis for designing a prospective study in ADPKD patients aimed to document the efficacy of sirolimus treatment in preventing further increase or even reducing the total kidney volume and the renal volume taken up by small cysts, eventually halting kidney disease progression. It is a 6 month treatment with sirolimus compared to conventional therapy in adult patients with ADPKD and normal renal function or mild to moderate renal insufficiency.

Conditions

  • Polycystic Kidney

Interventions

DRUG

Sirolimus

Patients will be given Sirolimus starting at the oral daily dose of 3 mg with periodically whole blood level measurements. The daily dose will be adjusted to keep sirolimus concentration within 10-15 ng/ml.

DRUG

conventional therapy

Antihypertensive drugs for patients with high blood pressure.

Sponsors & Collaborators

  • Mario Negri Institute for Pharmacological Research

    lead OTHER

Principal Investigators

  • Norberto Perico, MD · Mario Negri Institute for Pharmacological Research

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Max Age
80 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2007-03-31
Primary Completion
2009-07-31
Completion
2009-08-31

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00491517 on ClinicalTrials.gov