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Trial record 16 of 31 for:    Metreleptin

Recombinant Leptin Therapy for Treatment of Nonalcoholic Steatohepatitis (NASH)

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ClinicalTrials.gov Identifier: NCT00596934
Recruitment Status : Completed
First Posted : January 17, 2008
Results First Posted : December 9, 2016
Last Update Posted : November 24, 2017
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Michigan
Information provided by (Responsible Party):
Elif Oral, University of Michigan

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fatty Liver Disease, Nonalcoholic
Intervention Drug: metreleptin
Enrollment 9
Recruitment Details Patient recruitment occurred from February 2007 and concluded in October 2007.
Pre-assignment Details One of ten enrolled participants screen failed during baseline visit, liver biopsy showed no non-alcoholic steatohepatitis. Therefore he is not included in any tables or analyses.
Arm/Group Title NASH02
Hide Arm/Group Description

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Period Title: Overall Study
Started 9
Completed 7
Not Completed 2
Reason Not Completed
Protocol Violation             1
Withdrawal by Subject             1
Arm/Group Title Metreleptin Treatment Arm
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Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Baseline Participants 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 9 participants
44.3
(32 to 53)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants
Female
0
   0.0%
Male
9
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 9 participants
9
Non-alcoholic steatohepatitis (NASH) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 9 participants
8.1  (3.3)
[1]
Measure Description: NASH scale: 0 - 14. The higher the NASH score the more severe the liver disease.
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 9 participants
90.9  (9.0)
Liver fat percentage by Magnetic Resonance Imaging (MRI - Dixon method)   [1] 
Mean (Standard Deviation)
Unit of measure:  Liver fat percentage
Number Analyzed 9 participants
19.0  (7.7)
[1]
Measure Description: For determination of hepatic fat content by MRI and MR spectroscopy in patients, a series of out-phase and in-phase MRI at multiple flip angles are used. By combination of out-phase and in-phase MRI at multiple flip-angles and TE times, relaxation-time effects can be removed to yield quantitative intra-hepatic (and other organs’) fractional fat content throughout the liver in a few breath-hold intervals.
Liver function test: Alanine aminotransferase (ALT)   [1] 
Mean (Standard Deviation)
Unit of measure:  IU/L
Number Analyzed 9 participants
50.9  (19.4)
[1]
Measure Description: Normal range for laboratory values: <=35 IU/L
Liver function test: Aspartate aminotransferase (AST)   [1] 
Mean (Standard Deviation)
Unit of measure:  IU/L
Number Analyzed 9 participants
33.5  (13.3)
[1]
Measure Description: Normal range for laboratory values: 8 - 30 IU/L
Fasting glucose   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 9 participants
98.1  (7.2)
[1]
Measure Description: Normal range for laboratory values: 73 - 100 mg/dL
Insulin Resistance: homeostatic model assessment (HOMA)   [1] 
Mean (Standard Deviation)
Unit of measure:  mU/L x mg/dL
Number Analyzed 9 participants
7.4  (3.2)
[1]
Measure Description: HOMA values are based on fasting insulin and glucose concentrations and calculated as fasting insulin concentration (mU/L) x fasting glucose concentration (mg/dL)/405
Fasting triglycerides   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 9 participants
129.4  (66.2)
[1]
Measure Description: Normal range for laboratory values: <150 mg/dL
1.Primary Outcome
Title Non-alcoholic Steatohepatitis Score as Determined by Liver Histopathology at 12 Months
Hide Description Non-alcoholic steatohepatitis (NASH) score after approximately one year of treatment with metreleptin. Total NASH scores can range from 0 to 14. The higher the NASH score the more severe the liver disease.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Individuals who completed the year of metreleptin treatment and had follow-up liver biopsies after one year.
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
5  (1.73)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments Differences in each collected parameter will be evaluated using a paired t-test. If data are skewed such as in triglyceride levels, nonparametric tests will be used. P<0.05 will be considered significant. If a significant difference can be demonstrated between baseline and 1-year results, a large scale, placebo-controlled trial will be designed using the data obtained from this pilot study
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Body Weight at 12 Months
Hide Description Body weight (kg) after one year of treatment on metreleptin for patients that completed 12 months of metreleptin treatment.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Subjects that completed 12 months of metreleptin treatment.
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin: 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: kg
86.4  (9.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Liver Fat Percentage by Magnetic Resonance Imaging (MRI - Dixon Method) at 12 Months
Hide Description For determination of hepatic fat content by MRI and MR spectroscopy in patients, a series of out-phase and in-phase MRI at multiple flip angles are used. By combination of out-phase and in-phase MRI at multiple flip-angles and TE times, relaxation-time effects can be removed to yield quantitative intra-hepatic (and other organs’) fractional fat content throughout the liver in a few breath-hold intervals.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: liver fat percentage
13.7  (9.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments p = 0.074
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Liver Function Test: Alanine Aminotransferase (ALT) Values at 12 Months
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 subjects who completed 12 months of metreleptin treatment.
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: IU/L
44.3  (29.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Liver Function Test: Aspartate Aminotransferase (AST) Values at 12 Months
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 subjects who completed 12 months of metreleptin treatment.
Arm/Group Title Metreleptin Treatment Group
Hide Arm/Group Description:

Treatment group

metreleptin: 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: IU/L
34.9  (13.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Group
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Fasting Glucose Value at 12 Months
Hide Description Fasting glucose value in subjects that completed 12 months of metreleptin treatment.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 subjects who completed 12 months of metreleptin treatment.
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: mg/dL
92.1  (5.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Fasting Triglycerides Value at 12 Months
Hide Description Fasting triglyceride value in subjects that completed 12 months of metreleptin treatment.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 subjects who completed 12 months of metreleptin treatment.
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: mg/dL
146.4  (75.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.195
Comments p-value = 0.195.
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Insulin Resistance: Homeostatic Model Assessment (HOMA) at 12 Months
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
7 subjects who completed 12 months of metreleptin treatment.
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description:

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

Overall Number of Participants Analyzed 7
Mean (Standard Deviation)
Unit of Measure: mU/L x mg/dL
4.1  (3.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metreleptin Treatment Arm
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 13 months from patient baseline appointment.
Adverse Event Reporting Description Adverse event data collected from patient's baseline study appointment till one month following patient's 12 month study appointment.
 
Arm/Group Title Metreleptin Treatment Arm
Hide Arm/Group Description

Treatment group

metreleptin : 0.1 mg/kg/day once a day via subcutaneous injections

All-Cause Mortality
Metreleptin Treatment Arm
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Metreleptin Treatment Arm
Affected / at Risk (%) # Events
Total   1/9 (11.11%)    
Blood and lymphatic system disorders   
toxoplasmosis * [1]  1/9 (11.11%)  1
*
Indicates events were collected by non-systematic assessment
[1]
add description of advent.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Metreleptin Treatment Arm
Affected / at Risk (%) # Events
Total   1/9 (11.11%)    
Blood and lymphatic system disorders   
right sternocleidomastoid lymphadenopathy *  1/9 (11.11%)  1
right axilla lymphadenopathy *  1/9 (11.11%)  1
Musculoskeletal and connective tissue disorders   
left side muscle pain *  1/9 (11.11%)  1
Nervous system disorders   
vertigo *  1/9 (11.11%)  1
Renal and urinary disorders   
polyuria *  1/9 (11.11%)  1
haematuria *  1/9 (11.11%)  1
Reproductive system and breast disorders   
rectal pressure with ejaculation *  1/9 (11.11%)  1
Skin and subcutaneous tissue disorders   
actinic keratoses *  1/9 (11.11%)  10
*
Indicates events were collected by non-systematic assessment
This is a non-blinded, non-placebo controlled proof of concept trial. Out of the 9 patients, there were 7 completers.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Elif A. Oral
Organization: University of Michigan
Phone: 734-615-7271
Responsible Party: Elif Oral, University of Michigan
ClinicalTrials.gov Identifier: NCT00596934     History of Changes
Other Study ID Numbers: R03DK074488 ( U.S. NIH Grant/Contract )
R03DK074488 ( U.S. NIH Grant/Contract )
Protocol 2145 (MCRU)
Amylin Protocol 20050119
DRDA 643938K3
First Submitted: January 8, 2008
First Posted: January 17, 2008
Results First Submitted: August 22, 2016
Results First Posted: December 9, 2016
Last Update Posted: November 24, 2017