Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD): The Role of Biomarkers in Predicting a Response to Therapy

Study Overview
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Brief Summary
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Currently the only approved use for rapamycin (sirolimus) is for immunosuppression after renal transplantation. This trial is designed to determine whether rapamycin is safe and effective treatment for patients with polycystic kidney disease (ADPKD). Patients will be followed by volumetric magnetic resonance imaging (MRI) to observe for change in kidney (and cyst) size. Blood and urine samples will also be collected to evaluate for change in biomarkers with treatment.

Detailed Description
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This is a 2 year, open label trial to evaluate the role of rapamycin as treatment for ADPKD. Patients will be randomized 2:1 to the rapamycin arm or to standard therapy. The dose of rapamycin will be adjusted so that patients obtain 24 trough levels of 4-6ng/ml. There will be a volumetric MRI measurement at the start and end of the treatment period. Patients will be monitored every 4 months throughout the study.

Official Title
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Rapamycin as Treatment for ADPKD: The Role of Biomarkers in Predicting a Response to Therapy

Conditions
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Autosomal Dominant Polycystic Kidney Disease

Intervention / Treatment
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* Drug: Rapamycin
* Other: Standard of Care-Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult ADPKD patients aged 18-70 combined kidney volume >1200 ml estimated creatinine clearance >60 ml/min absence of implanted ferromagnetic objects Exclusion Criteria: Age >70 uncontrolled hyperlipidemia Proteinuria >500 mg/day unstable cerebral aneurysm active coronary artery disease diagnosis of another systemic condition affecting kidney function (ie: diabetes, hepatitis B or C, HIV) diagnosis of cancer other than skin cancer pregnancy or lactation presence of implanted ferromagnetic objects

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin<br>Drug: Rapamycin Other Names: sirolimus The starting dose of rapamycin will be 1 mg daily. The dose will be increased as needed to achieve a 24 hour trough level of 4-6 ng/ml. | Drug: Rapamycin<br>* The starting dose of rapamycin will be 1 mg daily. The dose will be increased as needed to achieve a 24 hour trough level of 4-6 ng/ml.<br>* Other names: sirolimus;|
| Placebo Comparator: Standard of Care-Placebo<br>Standard of Care | Other: Standard of Care-Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Kidney Volume (mL) |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular Filtration Rate (Kidney Function) |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autosomal Dominant Polycystic Kidney Disease, rapamycin, ADPKD