Sirolimus for Massive Polycystic Liver (SILVER)

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

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

Study Overview

• Status: Unknown
• Conditions: Polycystic Kidney Diseases
• Intervention / Treatment: Drug: Sirolimus

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 Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Recruiting
    • Seoul National University Hospital
    • Contact: Curie Ahn, MD, PhD; Phone Number: 82-2-2072-2222; Email: curie@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abdominal pain	Abdominal pain quantified by Visual Analog Scale	12month
Abdominal pain	Abdominal pain quantified by Visual Analog Scale	24 month
Infection	Incidence of infection event during study time	24 month
Hospitalization	Incidence of hospitalization due to adverse events during study time	24 month
Drop out	Incidence of discontinuation of study drug due to serious adverse events during study time	24 month

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer
• Investigators: Principal Investigator: Curie Ahn, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: September 3, 2012
• First Posted (Estimate): September 7, 2012

Study Record Updates

• Last Update Posted (Estimate): September 7, 2012
• Last Update Submitted That Met QC Criteria: September 3, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Liver cyst; Total liver volume
• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: Silver