Octreotide in Severe Polycystic Liver Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pilot Study Of Long-Acting Octreotide (Octreotide LAR® Depot) In The Treatment Of Patients With Severe Polycystic Liver Disease

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

Intervention / Treatment
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* Drug: Octreotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Octreotide<br>Participants received Octreotide LAR® Depot injections (up to 40 mg) intramuscularly every 28 days (+/- 5 days) for one year | Drug: Octreotide<br>* Participants received Octreotide LAR® Depot injections (up to 40 mg)intramuscularly every 28 days (+/- 5 days) for one year<br>* Other names: Octreotide LAR® Depot;|
| Placebo Comparator: Placebo<br>Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year | Drug: Placebo<br>* Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year<br>* Other names: Placebo injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Liver Volume | Percent change from baseline in liver volume, measured in milliliters by Magnetic Resonance Imaging (MRI)or Computed Tomography (CT) scans | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Renal Volume | Percent change from baseline in renal volume, measured in milliliters by MRI or CT scans | Baseline, 12 months | 
| Percent Change in Glomerular Filtration Rate (GFR) | Percent change from baseline in renal function/GFR, measured by clearance of iothalamate with monitoring of bladder emptying using ultrasound | Baseline, 12 months | 
| Change in Subject Reported Outcomes Using Mean Health Related Quality of Life (HRQoL) Scores | 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). | Baseline, 12 months |