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

Phase 3

Completed

• Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Interventions: Other: Standard; Drug: Sirolimus

• Registration Number: NCT00346918
• Lead Sponsor: University of Zurich

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2006-06
• Study First Submitted: 2006-06-22
• Study First Submitted QC: 2006-06-28
• Study First Posted: 2006-06-30
• Primary Completion: 2010-01
• Study Completion: 2010-06
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-26
• Last Update Posted: 2014-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Standard	Treatment of hypertension, cyst infections and flank pain
2	Sirolimus	Sirolimus plus Standard Treatment

Primary Outcome Measures

Name	Time	Method
renal volume measured by high resolution magnetic resolution imaging	1.5 yrs

Secondary Outcome Measures

Name	Time	Method
GFR	1.5 yrs
Adverse event	1.5 yrs

Trial Locations

Locations (1)

University Hospital; 🇨🇭 Zurich, Switzerland