Polycystic Kidney Diseases
Conditions
Keywords
Total liver volume, Liver cyst
Brief summary
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
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.
Interventions
DRUGSirolimus
Sirolimus administration for 12 months followed by conventional therapy alone for additional 12 months
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total liver volume | 12 months | Change in total liver volume |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total liver volume | 24 months | Change in total liver volume |
| Total kidney volume | 12 month | Change in total kidney volume |
| Estimated glomerular filtration rate | 12 month | Change in estimated glomerular filtration rate |
| Urinary biomarker | 12 month | Urinary biomarker level |
Other
| Measure | Time frame | Description |
|---|---|---|
| Infection | 24 month | Incidence of infection event during study time |
| Hospitalization | 24 month | Incidence of hospitalization due to adverse events during study time |
| Drop out | 24 month | Incidence of discontinuation of study drug due to serious adverse events during study time |
| Abdominal pain | 12month | Abdominal pain quantified by Visual Analog Scale |
Countries
South Korea
Contacts
Primary ContactCurie Ahn, MD, PhD
Outcome results
None listed