Sirolimus for Massive Polycystic Liver

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and safety of Sirolimus in reducing liver volume in autosomal dominant polycystic kidney disease.

Detailed Description
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Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of end stage renal disease (ESRD), affecting an estimated 0.2% of population. Of ADPKD patients, 58% in 15-24 year, 85% in 25-34 year, and 94% in 35-46 year olds suffer from polycystic liver in addition to polycystic kidneys. Several anti-proliferative drugs have been used in clinical trials to stop cyst growth both in liver and kidneys. Among them, octreotide and sirolimus have been shown to be one of the most promising drugs to reduce cyst volume. Sirolimus already has been used as one of the most potential oral immunosuppressants. Moreover, the serum trough level is quite easy to measure. Sirolimus is the mTOR inhibitor that has been proven to be effective in reducing cyst growth both in animal models. However, its efficacy and safety is not well proven in previous studies. This is a open-label, prospective study to evaluate the effectiveness and safety of Sirolimus to reduce cyst growth in ADPKD patients with massive polycystic liver.

Official Title
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An Open-label, Prospective Clinical Trial to Evaluate the Effectiveness and Safety of Sirolimus to Reduce Cyst Growth in ADPKD Patients With Massive Polycystic Liver

Conditions
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Polycystic Kidney Diseases

Intervention / Treatment
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* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 65 Patients diagnosed as ADPKD based upon the unified criteria for ultrasonographic diagnosis of ADPKD Polycystic liver with total liver volume > 2500 mL or symptomatic polycystic liver Estimated glomerular filtration rate (IDMS-traceable MDRD equation) >= 30 mL/min/1.73m2 Exclusion Criteria: Concomitant systemic renal parenchymal or urinary tract disease (random urine albumin-to-creatinine ratio > 500 mg/g) WBC < 4,000/uL, platelet < 100,000/uL, or hemoglobin < 10.0 g/dL Diabetes mellitus, cancer, or psychiatric disorder Increased liver enzymes (2-fold above normal value) Hypercholesterolemia (fasting cholesterol > 200mg/dL) or hypertriglyceridemia (>150 mg/dL) not controlled by lipid lowering therapy Infection with hepatitis B, C, HIV Any condition that could prevent full comprehension of the purpose and risks of the study Pregnant or lactating women or fertile women without effective contraception History of intervention, such as cyst aspiration or embolization in past 1 year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sirolimus<br>Sirolimus administration group starting dose: 2mg/day target trough level: 4-10 ng/dL | Drug: Sirolimus<br>* Sirolimus administration for 12 months followed by conventional therapy alone for additional 12 months<br>* Other names: Rapamune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total liver volume | Change in total liver volume | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total liver volume | Change in total liver volume | 24 months | 
| Total kidney volume | Change in total kidney volume | 12 month | 
| Estimated glomerular filtration rate | Change in estimated glomerular filtration rate | 12 month | 
| Urinary biomarker | Urinary biomarker level | 12 month | 
| Total kidney volume | Change in total kidney volume | 24 month | 
| Estimated glomerular filtration rate | Change in estimated glomerular filtration rate | 24 month | 
| Urinary biomarker | Urinary biomarker level | 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total liver volume, Liver cyst