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Treating Nonalcoholic Steatohepatitis (NASH) With Metformin

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ClinicalTrials.gov Identifier: NCT00063232
Recruitment Status : Completed
First Posted : June 24, 2003
Results First Posted : July 20, 2011
Last Update Posted : July 20, 2011
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis
Intervention Drug: Metformin
Enrollment 28
Recruitment Details 28 adult patients with biopsy-proven NASH were enrolled in the study and 26 completed the 48 weeks of therapy and underwent follow-up metabolic testing, imaging and repeat liver biopsy. 2 patients dropped out were not included in analyses.
Pre-assignment Details The two drop-outs included a 26-year-old woman who stopped therapy after 12 weeks because she had moved and her employment did not allow time for travel for outpatient visits and a 53-year-old woman who stopped therapy after 24 weeks because of desire to pursue other treatments.
Arm/Group Title Metformin
Hide Arm/Group Description Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
Period Title: Overall Study
Started 26
Completed 26
Not Completed 0
Arm/Group Title Metformin
Hide Arm/Group Description Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
Overall Number of Baseline Participants 26
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants
44  (14)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants
Female
13
  50.0%
Male
13
  50.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants
Non-Hispanic White 17
Hispanic White 4
Asian 5
African-American 0
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 26 participants
26
Body Mass Index  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants
Overweight (BMI=25-30 kg/m^2) 8
Obese (BMI=30-40 kg/m^2) 13
Severely Obese (BMI greater than 40 kg/m^2) 5
Glucose tolerance   [1] 
Measure Type: Number
Unit of measure:  Partcipants
Number Analyzed 26 participants
impaired 8
not impaired 18
[1]
Measure Description: Impaired glucose tolerance is defined by fasting glucose 110–125 or >=160 mg⁄ dL after 2-h glucose load
Diabetes   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 26 participants
Yes 7
No 19
[1]
Measure Description: Diabetes is defined by a fasting glucose greater or equal to 125 or greater or equal to 200 mg per dL aftera 2-h glucose load.
1.Primary Outcome
Title Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)
Hide Description Patients under went liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint is a three point improvement in the histological NASH activity index with a decrease in at least two of the component scores and no worsening of fibrosis or increase in Mallory bodies.
Time Frame from baseline to 48 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metformin
Hide Arm/Group Description:
Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
Overall Number of Participants Analyzed 26
Measure Type: Number
Unit of Measure: participants
improved (reduced) by greater or equal to 3 points 9
improved (reduced) by 1-2 points 11
no change 5
worsen (increased) 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin
Comments self-controlled comparison of NASH activity index at 48 weeks and baseline. Null hypothesis is "no change".
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
2.Secondary Outcome
Title Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)
Hide Description Alanine transaminase <42 U/L is considered normal
Time Frame from baseline to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metformin
Hide Arm/Group Description:
Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
Overall Number of Participants Analyzed 26
Measure Type: Number
Unit of Measure: participants
changed to normal from abnormal 9
unchanged (normal at beginning) 4
unchanged (abnormal at beginning) 12
changed to abnormal from normal 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin
Comments self-controlled comparison of serum aminotransferase levels at 48 weeks and baseline. Null hypothesis: No change
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline
Hide Description HOMA-IR is calculated from Fasting Glucose and Fasting Insulin
Time Frame from baseline to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Metformin
Hide Arm/Group Description:
Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: unit
-3.3  (3.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method paired t-test
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Metformin
Hide Arm/Group Description Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
All-Cause Mortality
Metformin
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Metformin
Affected / at Risk (%) # Events
Total   0/26 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Metformin
Affected / at Risk (%) # Events
Total   21/26 (80.77%)    
General disorders   
Weight loss  21/26 (80.77%)  21
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jay Hoofnagle, M.D.
Organization: National Institute of Diabetes and Digestive and Kidney Diseases
Phone: 3014961333
EMail: hoofnaglej@extra.niddk.nih.gov
Layout table for additonal information
Responsible Party: Jay Hoofnagle, M.D./National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00063232     History of Changes
Other Study ID Numbers: 030233
03-DK-0233
First Submitted: June 23, 2003
First Posted: June 24, 2003
Results First Submitted: March 14, 2011
Results First Posted: July 20, 2011
Last Update Posted: July 20, 2011