Sirolimus for Massive Polycystic Liver

Polycystic Kidney Diseases Clinical Trial

— SILVER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01680250
• Other study ID #: SILVER
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: August 30, 2012
• Last updated: September 3, 2012
• Start date: September 2011
• Est. completion date: August 2015

Study information

• Verified date: September 2012
• Source: Seoul National University Hospital
• Contact: Curie Ahn, MD, PhD
• Phone: 82-2-2072-2222
• Email: curie[@]snu.ac.kr
• Is FDA regulated: No
• Health authority: Korea: Food and Drug AdministrationKorea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: August 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Diseases
• Polycystic Kidney Diseases

Intervention

Drug:
• Sirolimus
Sirolimus administration for 12 months followed by conventional therapy alone for additional 12 months

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Abdominal pain	Abdominal pain quantified by Visual Analog Scale	12month	Yes
Other	Abdominal pain	Abdominal pain quantified by Visual Analog Scale	24 month	Yes
Other	Infection	Incidence of infection event during study time	24 month	Yes
Other	Hospitalization	Incidence of hospitalization due to adverse events during study time	24 month	Yes
Other	Drop out	Incidence of discontinuation of study drug due to serious adverse events during study time	24 month	Yes
Primary	Total liver volume	Change in total liver volume	12 months	No
Secondary	Total liver volume	Change in total liver volume	24 months	No
Secondary	Total kidney volume	Change in total kidney volume	12 month	No
Secondary	Estimated glomerular filtration rate	Change in estimated glomerular filtration rate	12 month	No
Secondary	Urinary biomarker	Urinary biomarker level	12 month	No
Secondary	Total kidney volume	Change in total kidney volume	24 month	No
Secondary	Estimated glomerular filtration rate	Change in estimated glomerular filtration rate	24 month	No
Secondary	Urinary biomarker	Urinary biomarker level	24 month	No