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Octreotide in Severe Polycystic Liver Disease

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT00426153
Collaborator
Novartis (Industry), National Center for Research Resources (NCRR) (NIH)
42
Enrollment
1
Location
2
Arms
21
Duration (Months)
2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Pilot Study Of Long-Acting Octreotide (Octreotide LAR® Depot) In The Treatment Of Patients With Severe Polycystic Liver Disease
Study Start Date :
Jan 1, 2007
Actual Primary Completion Date :
Oct 1, 2008
Actual Study Completion Date :
Oct 1, 2008

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Percent Change in Renal Volume [Baseline, 12 months]

      Percent change from baseline in renal volume, measured in milliliters by MRI or CT scans

    2. 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

    3. 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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic
    • Novartis
    • National Center for Research Resources (NCRR)

    Investigators

    • Principal Investigator: Marie C. Hogan, M.D., Ph.D., Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Marie Hogan, MD, PhD, Assistant Professor of Medicine, College of Medicine, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT00426153
    Other Study ID Numbers:
    • 06-004128
    • UL1RR024150
    First Posted:
    Jan 24, 2007
    Last Update Posted:
    Nov 21, 2012
    Last Verified:
    Oct 1, 2012
    Additional relevant MeSH terms:
    Cysts
    Liver Diseases
    Hepatomegaly
    Polycystic Kidney Diseases
    Polycystic Kidney, Autosomal Dominant
    Abdominal Pain
    Octreotide

    Study Results

    Participant Flow

    Recruitment Details 42 participants were enrolled at Mayo Clinic in Rochester, Minnesota from 1/1/2007 to 5/19/2008.
    Pre-assignment Detail Following consent a tolerability test dose of 100 micrograms of short-acting octreotide was administered subcutaneously to subjects, followed by 4 hours of observation/vital signs. Randomized intramuscular dosing began the next day.
    Arm/Group Title Octreotide Placebo
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year
    Period Title: Overall Study
    STARTED 28 14
    COMPLETED 28 14
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Octreotide Placebo Total
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year Total of all reporting groups
    Overall Participants 28 14 42
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    49.7
    (9)
    50.3
    (7.3)
    49.9
    (8.4)
    Sex: Female, Male (Count of Participants)
    Female
    23
    82.1%
    13
    92.9%
    36
    85.7%
    Male
    5
    17.9%
    1
    7.1%
    6
    14.3%
    Region of Enrollment (participants) [Number]
    United States
    28
    100%
    14
    100%
    42
    100%
    Glomerular Filtration Rate (milliliters/minute per 1.73 m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milliliters/minute per 1.73 m^2]
    70
    (27)
    71
    (27)
    70
    (27)
    Body Mass Index (kilograms/meter^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms/meter^2]
    26.3
    (5.77)
    24.4
    (2.98)
    25.7
    (5.0)
    Body Weight (kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms]
    76.0
    (20.2)
    70.9
    (10.9)
    74.3
    (17.8)
    Serum creatinine (milligrams/deciliter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams/deciliter]
    1.1
    (0.4)
    1.1
    (0.5)
    1.1
    (0.5)
    Fasting plasma glucose (milligrams/deciliter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams/deciliter]
    93.4
    (11.2)
    93.6
    (7.8)
    93.5
    (10.1)
    Urine Albumin (milligrams/24 hours) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milligrams/24 hours]
    65
    (123)
    130
    (237)
    87
    (171)
    Systolic Blood Pressure (millimeters of mercury (mmHg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimeters of mercury (mmHg)]
    122.1
    (13.2)
    120.5
    (13.5)
    121.6
    (13.2)
    Diastolic Blood Pressure (millimeters of mercury (mmHg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimeters of mercury (mmHg)]
    79.8
    (8.9)
    79.1
    (9.2)
    79.6
    (8.9)
    Liver volume (milliliters (ml)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milliliters (ml)]
    5907.7
    (2915.0)
    5373.9
    (3565.4)
    5729.8
    (3113.1)
    Kidney volume (milliliters (ml)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [milliliters (ml)]
    1142.9
    (826.9)
    803.0
    (269.1)
    1049.2
    (728.3)
    Genotypes and genetic mutations (Number) [Number]
    ADPKD genotype with PKD1 gene mutation
    16
    57.1%
    9
    64.3%
    25
    59.5%
    ADPKD genotype with PKD2 gene mutation
    5
    17.9%
    1
    7.1%
    6
    14.3%
    ADPKD genotype with no genetic mutation detected
    3
    10.7%
    0
    0%
    3
    7.1%
    ADPLD genotype with PRKCSH gene mutation
    3
    10.7%
    1
    7.1%
    4
    9.5%
    ADPLD genotype with SEC63 gene mutation
    0
    0%
    1
    7.1%
    1
    2.4%
    ADPLD genotype with no genetic mutation detected
    1
    3.6%
    2
    14.3%
    3
    7.1%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Octreotide Placebo
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year
    Measure Participants 28 14
    Mean (Standard Deviation) [percent change]
    -5.0
    (6.77)
    0.9
    (8.33)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Octreotide, Placebo
    Comments P values <0.05 were considered statistically significant.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.048
    Comments
    Method Rank-sum test
    Comments
    2. Secondary Outcome
    Title Percent Change in Renal Volume
    Description Percent change from baseline in renal volume, measured in milliliters by MRI or CT scans
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    13 subjects were excluded from the analysis of the kidney data: 4 subjects had renal transplant before enrollment (3 in octreotide and 1 in placebo groups), 8 subjects had a diagnosis of ADPLD (4 in each group), 1 placebo subject has missing kidney data due to incomplete image coverage.
    Arm/Group Title Octreotide Placebo
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year
    Measure Participants 21 8
    Mean (Standard Deviation) [percent change]
    0.25
    (7.53)
    8.61
    (10.07)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Octreotide, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.045
    Comments P values < 0.05 were considered statistically significant
    Method Rank sum
    Comments
    3. Secondary Outcome
    Title Percent Change in Glomerular Filtration Rate (GFR)
    Description Percent change from baseline in renal function/GFR, measured by clearance of iothalamate with monitoring of bladder emptying using ultrasound
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    13 subjects were excluded from the analysis of the kidney data: 4 subjects had renal transplant before enrollment (3 in octreotide and 1 in placebo groups), 8 subjects had a diagnosis of ADPLD (4 in each group), 1 placebo subject has missing kidney data due to incomplete image coverage.
    Arm/Group Title Octreotide Placebo
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year
    Measure Participants 21 8
    Mean (Standard Deviation) [percent change]
    -5.1
    (15.46)
    -7.2
    (13.21)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Octreotide, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.98
    Comments P Values < 0.05 were considered statistically significant
    Method Rank sum
    Comments
    4. Secondary Outcome
    Title Change in Subject Reported Outcomes Using Mean Health Related Quality of Life (HRQoL) Scores
    Description 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).
    Time Frame Baseline, 12 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Octreotide Placebo
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year
    Measure Participants 24 12
    Physical functioning at baseline
    74.8
    (21.96)
    80.4
    (23.73)
    Physical functioning at 12 months
    77.0
    (21.32)
    82.1
    (18.58)
    Physical role at baseline
    59.8
    (42.13)
    76.8
    (39.79)
    Physical role at 12 months
    74.1
    (35.00)
    75.0
    (41.60)
    Bodily Pain at baseline
    67.8
    (15.29)
    65.5
    (24.25)
    Bodily pain at 12 months
    75.7
    (19.02)
    68.7
    (25.51)
    General health at baseline
    55.9
    (21.29)
    58.0
    (23.63)
    General health at 12 months
    53.5
    (17.32)
    63.4
    (23.96)
    Vitality at baseline
    49.6
    (21.81)
    53.9
    (25.96)
    Vitality at 12 months
    54.4
    (24.23)
    54.6
    (27.91)
    Social functioning at baseline
    79.0
    (19.56)
    75.0
    (27.30)
    Social functioning at 12 months
    82.9
    (19.35)
    81.3
    (21.79)
    Emotional role at baseline
    82.1
    (32.05)
    73.8
    (37.39)
    Emotional role at 12 month
    91.4
    (23.74)
    81.0
    (38.60)
    Mental health at baseline
    76.0
    (14.12)
    75.4
    (18.75)
    Mental health at 12 months
    76.9
    (16.54)
    80.7
    (18.76)
    Standardized physical component at baseline
    42.6
    (9.73)
    46.0
    (10.16)
    Standardized physical component at 12 months
    44.7
    (10.00)
    46.1
    (9.51)
    Standardized mental component at baseline
    50.8
    (7.74)
    48.4
    (10.96)
    Standardized mental component at 12 month
    52.2
    (8.03)
    51.3
    (11.15)

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description
    Arm/Group Title Octreotide Placebo
    Arm/Group Description Participants received Octreotide LAR® Depot injections intramuscularly every 28 days (+/- 5 days) for one year Participants received an injection of placebo (sham) medication intramuscularly every 28 days (+/- 5 day) for one year
    All Cause Mortality
    Octreotide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Octreotide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/28 (10.7%) 0/14 (0%)
    Gastrointestinal disorders
    Abdominal hernia, incarcerated 1/28 (3.6%) 1 0/14 (0%) 0
    Renal and urinary disorders
    Bacteremia 1/28 (3.6%) 1 0/14 (0%) 0
    Urinary tract infection 1/28 (3.6%) 1 0/14 (0%) 0
    Other (Not Including Serious) Adverse Events
    Octreotide Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/28 (75%) 4/14 (28.6%)
    Gastrointestinal disorders
    Diarrhea, Grade 1 17/28 (60.7%) 17 4/14 (28.6%) 4
    Steatorrhea & weight loss 1/28 (3.6%) 1 0/14 (0%) 0
    abdominal cramping, bloating and gas 14/28 (50%) 14 4/14 (28.6%) 4
    Skin and subcutaneous tissue disorders
    Alopecia, moderate 1/28 (3.6%) 1 0/14 (0%) 0
    Injection site granuloma 5/28 (17.9%) 5 0/14 (0%) 0
    Injection site pain 21/28 (75%) 21 3/14 (21.4%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Marie Hogan, MD, PhD, Assistant Prof of Medicine, College of Medicine
    Organization Mayo Clinic
    Phone 507-266-9364
    Email hogan.marie@mayo.edu
    Responsible Party:
    Marie Hogan, MD, PhD, Assistant Professor of Medicine, College of Medicine, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT00426153
    Other Study ID Numbers:
    • 06-004128
    • UL1RR024150
    First Posted:
    Jan 24, 2007
    Last Update Posted:
    Nov 21, 2012
    Last Verified:
    Oct 1, 2012