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Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy

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ClinicalTrials.gov Identifier: NCT01679197
Recruitment Status : Completed
First Posted : September 5, 2012
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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
Conditions Fatty Liver Disease, Nonalcoholic
Nonalcoholic Steatohepatitis
Lipodystrophy
Intervention Drug: Metreleptin
Enrollment 23
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment
Hide Arm/Group Description

Metreleptin

Metreleptin

Period Title: Overall Study
Started 23
Completed 19
Not Completed 4
Arm/Group Title Treatment
Hide Arm/Group Description

Metreleptin

Metreleptin

Overall Number of Baseline Participants 23
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
<=18 years
3
  13.0%
Between 18 and 65 years
20
  87.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants
42.35  (15.82)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
18
  78.3%
Male
5
  21.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Caucasian
22
  95.7%
African American
1
   4.3%
Asian
0
   0.0%
Native American
0
   0.0%
Unknown
0
   0.0%
Decline to answer
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 23 participants
23
1.Primary Outcome
Title Liver Histopathology
Hide Description Primary outcome will be the total non-alcoholic steatohepatitis (NASH) score read histopathologically from the liver biopsy samples. This outcome measure quantifies the severity of fatty liver disease. At baseline and at the end of the year, patients have undergone a transcutaneous liver biopsy and the specimens were graded for the severity of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) pathology. Histological features of NAFLD/NASH were scored using the validated NASH-CRN (NASH Clinical Research Network) scoring system. This scoring system is the total of 4 subscales: steatosis (0-3), lobular inflammation (0-3), hepatocellular ballooning (0-2) and fibrosis (0-4), which are evaluated semi-quantitatively. The total scale range for this scoring system is 0-12, with 0 representing no features of fatty liver disease, and 12 representing the highest degree of fatty liver disease.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.
Arm/Group Title Treatment
Hide Arm/Group Description:

Metreleptin

Metreleptin

Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 23 participants
6  (2)
Month 12 Number Analyzed 19 participants
5  (2)
2.Secondary Outcome
Title Liver Fat by MRI and MR Spectroscopy
Hide Description All enrolled patients will have a baseline MRI of the liver to evaluate liver volume and liver fat. 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.
Arm/Group Title Treatment
Hide Arm/Group Description:

Metreleptin

Metreleptin

Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: %fat
Baseline Number Analyzed 23 participants
19.19  (11.11)
Month 12 Number Analyzed 19 participants
13.47  (9.02)
3.Secondary Outcome
Title Liver Function Tests
Hide Description AST and ALT are the liver function tests. We are reporting the liver function tests where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.
Arm/Group Title Liver Function AST Liver Function ALT
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: IU/L
Baseline Number Analyzed 23 participants 23 participants
41.52  (27.46) 53.22  (37.03)
Month 12 Number Analyzed 19 participants 19 participants
30.37  (14.04) 36  (22.84)
4.Secondary Outcome
Title Fasting Lipids
Hide Description Cholesterol, triglycerides, HDL cholesterol, and LDL together make up the lipid profile and must be reported together. We are reporting the lipid profile where the treatment group arm would normally be listed, though, we are looking at the same single arm population of 23 participants who received treatment in this study.
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.
Arm/Group Title Cholesterol, Total mg/dL Triglycerides mg/dL HDL Cholesterol mg/dL LDL mg/dL
Hide Arm/Group Description:
Lipid measurement
Lipid measurement
Lipid measurement
Lipid measurement
Overall Number of Participants Analyzed 23 23 23 23
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline Number Analyzed 23 participants 23 participants 23 participants 23 participants
256.91  (136.87) 1057.48  (1744.89) 35.83  (11.01) 95.39  (48.30)
Month 12 Number Analyzed 19 participants 19 participants 19 participants 19 participants
189.11  (64.73) 478.47  (790.85) 33.42  (6.41) 95.95  (32.64)
5.Secondary Outcome
Title Fasting Glucose
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants analyzed at month 12 differs from the overall number analyzed at baseline because 4 participants dropped from the study before their month 12 visit.
Arm/Group Title Treatment
Hide Arm/Group Description:

Metreleptin

Metreleptin

Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline Number Analyzed 23 participants
178.91  (82.36)
Month 12 Number Analyzed 19 participants
163.53  (66.79)
6.Secondary Outcome
Title Body Weight
Hide Description [Not Specified]
Time Frame 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment
Hide Arm/Group Description:

Metreleptin

Metreleptin

Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: kg
Baseline 77.2  (21.4)
Month 12 75.0  (23.1)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment
Hide Arm/Group Description

Metreleptin

Metreleptin

All-Cause Mortality
Treatment
Affected / at Risk (%)
Total   0/23 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment
Affected / at Risk (%) # Events
Total   7/23 (30.43%)    
Cardiac disorders   
Left shoulder pain, atypical chest pain   1/23 (4.35%)  1
Gastrointestinal disorders   
Epigastric pain, mild chest pain   1/23 (4.35%)  1
Immune system disorders   
Granulomatous tissue reaction   1/23 (4.35%)  1
Metabolism and nutrition disorders   
Hypertriglyceridemia   1/23 (4.35%)  1
Secondary diabetes mellitus with keatoacidosis   1/23 (4.35%)  1
Musculoskeletal and connective tissue disorders   
Fall, hip fracture   1/23 (4.35%)  1
Chest pain   1/23 (4.35%)  1
Nervous system disorders   
Transient ischemic attack vs. cerebrovascular attack vs. complicated migraine   1/23 (4.35%)  1
Bell's palsy left side weakness   1/23 (4.35%)  1
Renal and urinary disorders   
UTI abdominal pain   1/23 (4.35%)  1
Respiratory, thoracic and mediastinal disorders   
Bronchial pneumonia   1/23 (4.35%)  1
Surgical and medical procedures   
Rectal prolapse surgery   1/23 (4.35%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment
Affected / at Risk (%) # Events
Total   22/23 (95.65%)    
Blood and lymphatic system disorders   
Hypoglycemia   7/23 (30.43%)  12
Gastrointestinal disorders   
Diarrhea   5/23 (21.74%)  6
Vomiting   2/23 (8.70%)  3
Abdominal pain/discomfort   3/23 (13.04%)  3
General disorders   
Dizziness   2/23 (8.70%)  2
Nausea   3/23 (13.04%)  4
Immune system disorders   
Upper respiratory tract infection   9/23 (39.13%)  10
Infections and infestations   
Cold/Flu-like symptoms   4/23 (17.39%)  4
Musculoskeletal and connective tissue disorders   
Muscle cramping   2/23 (8.70%)  2
Fall   2/23 (8.70%)  2
Renal and urinary disorders   
Urinary tract infection   2/23 (8.70%)  3
Hematuria   2/23 (8.70%)  2
Respiratory, thoracic and mediastinal disorders   
Bronchitis   2/23 (8.70%)  2
Asthma   3/23 (13.04%)  3
Cough   2/23 (8.70%)  2
Skin and subcutaneous tissue disorders   
Alopecia   2/23 (8.70%)  2
Injection site reaction   3/23 (13.04%)  3
Rash   2/23 (8.70%)  2
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT 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: Dr. Elif Oral
Organization: University of Michigan
Phone: 7346157271
Responsible Party: Elif Oral, University of Michigan
ClinicalTrials.gov Identifier: NCT01679197     History of Changes
Other Study ID Numbers: MCRU 2834
R01DK088114-02 ( U.S. NIH Grant/Contract )
First Submitted: August 31, 2012
First Posted: September 5, 2012
Results First Submitted: March 28, 2017
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017