Clinical trial NCT01680250: Sirolimus for Massive Polycystic Liver
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Polycystic Kidney Diseases
Keywords: Total liver volume
Liver cyst
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2012-09-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total liver volume
timeFrame: 12 months
Secondary outcomes:
measure: Total liver volume
timeFrame: 24 months
measure: Total kidney volume
timeFrame: 12 month
measure: Estimated glomerular filtration rate
timeFrame: 12 month
measure: Urinary biomarker
timeFrame: 12 month
measure: Total kidney volume
timeFrame: 24 month
measure: Estimated glomerular filtration rate
timeFrame: 24 month
measure: Urinary biomarker
timeFrame: 24 month
Other outcomes:
measure: Abdominal pain
timeFrame: 12month
measure: Abdominal pain
timeFrame: 24 month
measure: Infection
timeFrame: 24 month
measure: Hospitalization
timeFrame: 24 month
measure: Drop out
timeFrame: 24 month
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Curie Ahn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: