Trial Outcomes & Findings for Treating Nonalcoholic Steatohepatitis (NASH) With Metformin (NCT NCT00063232)
NCT ID: NCT00063232
Last Updated: 2011-07-20
Results Overview
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.
COMPLETED
PHASE2
28 participants
from baseline to 48 Weeks
2011-07-20
Participant Flow
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.
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.
Participant milestones
| Measure |
Metformin
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.
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|---|---|
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Overall Study
STARTED
|
26
|
|
Overall Study
COMPLETED
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treating Nonalcoholic Steatohepatitis (NASH) With Metformin
Baseline characteristics by cohort
| Measure |
Metformin
n=26 Participants
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.
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|---|---|
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Age Continuous
|
44 years
STANDARD_DEVIATION 14 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
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Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic White
|
17 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic White
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
0 participants
n=5 Participants
|
|
Region of Enrollment
United States
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26 participants
n=5 Participants
|
|
Body Mass Index
Overweight (BMI=25-30 kg/m^2)
|
8 participants
n=5 Participants
|
|
Body Mass Index
Obese (BMI=30-40 kg/m^2)
|
13 participants
n=5 Participants
|
|
Body Mass Index
Severely Obese (BMI greater than 40 kg/m^2)
|
5 participants
n=5 Participants
|
|
Glucose tolerance
impaired
|
8 partcipants
n=5 Participants
|
|
Glucose tolerance
not impaired
|
18 partcipants
n=5 Participants
|
|
Diabetes
Yes
|
7 participants
n=5 Participants
|
|
Diabetes
No
|
19 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: from baseline to 48 WeeksPatients 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.
Outcome measures
| Measure |
Metformin
n=26 Participants
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.
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|---|---|
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Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)
improved (reduced) by greater or equal to 3 points
|
9 participants
|
|
Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)
improved (reduced) by 1-2 points
|
11 participants
|
|
Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)
no change
|
5 participants
|
|
Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)
worsen (increased)
|
1 participants
|
SECONDARY outcome
Timeframe: from baseline to 48 weeksAlanine transaminase \<42 U/L is considered normal
Outcome measures
| Measure |
Metformin
n=26 Participants
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.
|
|---|---|
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Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)
changed to normal from abnormal
|
9 participants
|
|
Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)
unchanged (normal at beginning)
|
4 participants
|
|
Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)
unchanged (abnormal at beginning)
|
12 participants
|
|
Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)
changed to abnormal from normal
|
1 participants
|
SECONDARY outcome
Timeframe: from baseline to 48 weeksHOMA-IR is calculated from Fasting Glucose and Fasting Insulin
Outcome measures
| Measure |
Metformin
n=26 Participants
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.
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|---|---|
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Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline
|
-3.3 unit
Standard Deviation 3.2
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Adverse Events
Metformin
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Metformin
n=26 participants at risk
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.
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|---|---|
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General disorders
Weight loss
|
80.8%
21/26 • Number of events 21
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Additional Information
Jay Hoofnagle, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place