Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

University of Zurich (UZH)

Status and phase

Completed

Phase 3

Conditions

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Treatments

Drug: Sirolimus

Other: Standard

Study type

Interventional

Funder types

Other

Identifiers

NCT00346918

EK-1246

Details and patient eligibility

About

The aim of our study is to investigate whether Rapamune used at a low dose (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD.

Full description

Currently there is no treatment for ADPKD other than supportive care and blood pressure control. Usually dialytic treatment or renal transplantation becomes necessary when the disease has progressed to end-stage renal failure.We and others could demonstrate that rapamycin, a classical mTOR inhibitor, retards cyst growth and preserves renal function in a rodent model of ADPKD. The aim of our study is to investigate whether Rapamune (2 mg/d) retards cyst growth and slows renal functional deterioration in patients with ADPKD. We anticipate that we can slow disease progression and delay the need for chronic renal replacement therapy by the inhibition of mTOR with Rapamune. This is a 24-month prospective, controlled, open label study with 2 parallel groups in patients with ADPKD. Patients will be randomized at a 1:1 ratio to one of the 2 treatment arms. Primary endpoint is percentage change of renal volume measured by high resolution magnetic resolution imaging.

Enrollment

100 patients

Sex

All

Ages

18 to 40 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female ADPKD patient between 18 and 40 years of age
measured GFR higher than 70 ml/min 1.73m2
documented kidney volume progression
informed consent

Exclusion criteria

Female of childbearing potential who is planning to become pregnant, who is pregnant and/or lactating, who is unwilling to use effective means of contraception
increased liver enzymes (2-fold above normal values)
hypercholesterolemia (fasting cholesterol > 8 mmol/l) or hypertriglyceridaemia (> 5 mmol/l) not controlled by lipid lowering therapy
granulocytopenia (white blood cell < 3,000/mm3) or thrombocytopenia (platelets < 100,000/mm3),
infection with hepatitis B or C, HIV
any past or present malignancy
mental illness that interfere with the patient ability to comply with the protocol
drug or alcohol abuse within one year of baseline
co-medication with strong inhibitor of CYP3A4 and or P-gp like voriconazole, ketoconazole, diltiazem, verapamil, erythromycin
co-medication with strong CYP3A4 and or P-gp inductor like rifampicin
known hypersensitivity to macrolides or Rapamune