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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Sirolimus (Rapamune®) for Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD): a Randomized Controlled Study.

Conditions
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Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Intervention / Treatment
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* Drug: Sirolimus
* Other: Standard


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Treatment of hypertension, cyst infections and flank pain | Other: Standard<br>* Standard<br>* Other names: Treatment of hypertension, cyst infections and flank pain;|
| Active Comparator: 2<br>Sirolimus plus Standard Treatment | Drug: Sirolimus<br>* Standard plus Sirolimus<br>* Other names: Rapamune (R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| renal volume measured by high resolution magnetic resolution imaging |  | 1.5 yrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GFR |  | 1.5 yrs | 
| Adverse event |  | 1.5 yrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADPKD, autosomal dominant polycystic kidney disease, Sirolimus, volumetry