Octreotide in Severe Polycystic Liver Disease

Phase 2

Completed

Conditions: Polycystic Kidney, Autosomal Dominant
Polycystic Liver Disease
Hepatomegaly
Liver Diseases
Kidney, Polycystic
Abdominal Pain

Brief Summary: This study will evaluate the effect of Octreotide LAR® on the liver volumes of patients with severe polycystic liver disease who are not candidates or decline surgical treatments such as liver cyst fenestration, liver resection or liver transplantation. A total of 42 patients will be recruited -14 who will receive placebo and 28 the study drug. Preliminary evidence indicates that this drug is safe and non-toxic in other disease states. Treatment with this drug holds promise not only for individuals with liver involvement, but also for many more patients with polycystic kidney disease.

Detailed Description: The primary aim of this study is to compare the effect of Octreotide LAR® Depot on the liver volume of patients with severe polycystic liver disease who are not candidates or decline surgical treatments such as liver cyst fenestration, liver resection or liver transplantation compared with placebo. The secondary aims of the study are: (1)Assess the effect of Octreotide LAR® Depot on the total kidney volume and iothalamate clearance in patients with polycystic kidney disease associated with severe polycystic liver disease who are not candidates or decline surgical treatments such as liver cyst fenestration, liver resection or liver transplantation. (2)Evaluate quality of life changes associated with the administration of Octreotide LAR® Depot in these patients. (3)Assess toxicity of Octreotide LAR® Depot in patients with polycystic liver disease (PLD).

Note: Subjects who completed this 1 year randomized trial were offered enrollment into an open-label (all subjects received Octreotide) extension trial for an additional two years of treatment.

Recruitment & Eligibility

Inclusion Criteria

Age - 18 years and older
Diagnosis of Polycystic Liver Disease (PLD) associated with ADPKD or isolated Autosomal Dominant Polycystic liver Disease (ADPLD)
Severe PLD defined as a liver volume greater than 4000 mL or symptomatic disease due to mass effects from hepatic cysts
Not a candidate for or declining surgical intervention

Exclusion Criteria

Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception
Creatinine greater than 3mg/dL or hemodialysis dependent
Cancer or major systemic disease that could prevent completion of the planned follow-up or interfere with data collection or interpretation
Uncontrolled diabetes mellitus as defined by blood glucose levels of greater than or equal to 250 mg/dL on 2 or more consecutive daily readings despite antidiabetic therapy
Neurologic/psychologic conditions preventing appropriate informed consent
Symptomatic gallstones or biliary sludge
Variceal bleeding or hepatic encephalopathy within prior 30 days
Uncontrolled hypertension (Systolic blood pressure greater than 160 mmHg; Diastolic blood pressure greater than 100 mmHg)
Current, or prior use of somatostatin analogue (octreotide, lanreotide) in past 6 months
History of significant adverse reaction to a somatostatin analogue

Arm && Interventions

Group	Intervention	Description
Octreotide	Octreotide	Participants received Octreotide LAR® Depot injections (up to 40 mg) intramuscularly every 28 days (+/- 5 days) for one year
Placebo	Placebo	Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year

Primary Outcome Measures

Name	Time	Method
Percent Change in Liver Volume	Baseline, 12 months	Percent change from baseline in liver volume, measured in milliliters by Magnetic Resonance Imaging (MRI)or Computed Tomography (CT) scans

Secondary Outcome Measures

Name	Time	Method
Percent Change in Renal Volume	Baseline, 12 months	Percent change from baseline in renal volume, measured in milliliters by MRI or CT scans
Percent Change in Glomerular Filtration Rate (GFR)	Baseline, 12 months	Percent change from baseline in renal function/GFR, measured by clearance of iothalamate with monitoring of bladder emptying using ultrasound
Change in Subject Reported Outcomes Using Mean Health Related Quality of Life (HRQoL) Scores	Baseline, 12 months	Scores on the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), version 2. Subjects completed the SF-36 which consists of 8 sub-scales which are additionally summarized into 2 summary components (physical and mental). The subscales and the summary scales both range from 0 to 100, with (0 = worst imaginable, 100 = best imaginable).