Octreotide in Severe Polycystic Liver Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Liver Diseases; Abdominal Pain; Polycystic Kidney, Autosomal Dominant; Hepatomegaly; Polycystic Liver Disease; Kidney, Polycystic
• Intervention / Treatment: Drug: Octreotide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Novartis; National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Marie C. Hogan, M.D., Ph.D., Mayo Clinic

Publications and helpful links

General Publications

• Hogan MC, Masyuk TV, Page L, Holmes DR 3rd, Li X, Bergstralh EJ, Irazabal MV, Kim B, King BF, Glockner JF, Larusso NF, Torres VE. Somatostatin analog therapy for severe polycystic liver disease: results after 2 years. Nephrol Dial Transplant. 2012 Sep;27(9):3532-9. doi: 10.1093/ndt/gfs152. Epub 2012 Jul 6.
• Hogan MC, Masyuk T, Bergstralh E, Li B, Kremers WK, Vaughan LE, Ihrke A, Severson AL, Irazabal MV, Glockner J, LaRusso NF, Torres VE. Efficacy of 4 Years of Octreotide Long-Acting Release Therapy in Patients With Severe Polycystic Liver Disease. Mayo Clin Proc. 2015 Aug;90(8):1030-7. doi: 10.1016/j.mayocp.2015.05.011. Epub 2015 Jul 9.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: January 22, 2007
• First Submitted That Met QC Criteria: January 23, 2007
• First Posted (Estimate): January 24, 2007

Study Record Updates

• Last Update Posted (Estimate): November 21, 2012
• Last Update Submitted That Met QC Criteria: October 22, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Kidney Diseases; Urologic Diseases; Pain; Neurologic Manifestations; Congenital Abnormalities; Signs and Symptoms, Digestive; Genetic Diseases, Inborn; Pathological Conditions, Anatomical; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Hypertrophy; Liver Diseases; Abdominal Pain; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Cysts; Hepatomegaly; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: 06-004128; UL1RR024150 (U.S. NIH Grant/Contract)