Sirolimus for Massive Polycystic Liver

Phase 2

• Conditions: Polycystic Kidney Diseases
• Interventions: Drug: Sirolimus

• Registration Number: NCT01680250
• Lead Sponsor: Seoul National University Hospital

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.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2012-08-30
• Status Verified: 2012-09
• Study First Submitted QC: 2012-09-03
• Last Update Submitted: 2012-09-03
• Study First Posted: 2012-09-07
• Last Update Posted: 2012-09-07
• Primary Completion: 2014-09
• Study Completion: 2015-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sirolimus	Sirolimus	Sirolimus administration group starting dose: 2mg/day target trough level: 4-10 ng/dL

Primary Outcome Measures

Name	Time	Method
Total liver volume	12 months	Change in total liver volume

Secondary Outcome Measures

Name	Time	Method
Total kidney volume	24 month	Change in total kidney volume
Estimated glomerular filtration rate	24 month	Change in estimated glomerular filtration rate
Urinary biomarker	24 month	Urinary biomarker level
Total liver volume	24 months	Change in total liver volume

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of