Trial Outcomes & Findings for Prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) in Hispanics With Diabetes Mellitus Type 2 (T2DM) and Role of Treatment (NCT NCT01002547)
NCT ID: NCT01002547
Last Updated: 2018-09-11
Results Overview
Number of patients with reduction of at least 2 points in the nonalcoholic fatty liver disease activity score (NAS) (with reduction in at least 2 different histological categories) without worsening of fibrosis. NAS is the sum of the separate scores for steatosis (0-3), hepatocellular ballooning (0-2) and lobular inflammation (0-3), and ranges from 0-8 . The scoring system is based on the following grading: Steatosis: 0 = \<5%; 1 = 5-33%; 2 = \>33-66%; 3 = \>66%. Lobular Inflammation: 0 = No foci 1 = \<2 foci/200x; 2 = 2-4 foci/200x, 3 = \>4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
105 participants
Primary outcome timeframe
18 months
Results posted on
2018-09-11
Participant Flow
Subjects were recruited from the endocrinology and hepatology clinics at two VA Medical Centers (i.e., Audie L. Murphy in San Antonio, TX and Malcom Randall in Gainesville, FL). The study was conducted between June 2010 and September 2016 (recruitment was completed in December 2014).
After initial screening (medical history, physical exam, laboratories, 75-gram oral glucose tolerance test \[OGTT\]), patients were instructed to keep physical activity and diet constant during the run-in phase (mean duration: 1 month).
Participant milestones
| Measure |
Placebo
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Overall Study
STARTED
|
32
|
36
|
37
|
|
Overall Study
COMPLETED
|
24
|
33
|
29
|
|
Overall Study
NOT COMPLETED
|
8
|
3
|
8
|
Reasons for withdrawal
| Measure |
Placebo
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
0
|
5
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
0
|
|
Overall Study
Death
|
0
|
2
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
Baseline Characteristics
Prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) in Hispanics With Diabetes Mellitus Type 2 (T2DM) and Role of Treatment
Baseline characteristics by cohort
| Measure |
Placebo
n=32 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
57 years
STANDARD_DEVIATION 11 • n=5 Participants
|
60 years
STANDARD_DEVIATION 9 • n=7 Participants
|
60 years
STANDARD_DEVIATION 6 • n=5 Participants
|
59 years
STANDARD_DEVIATION 9 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
93 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
23 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
76 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
African American
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
|
Body mass index
|
33.6 kg/m2
STANDARD_DEVIATION 4.0 • n=5 Participants
|
33.8 kg/m2
STANDARD_DEVIATION 4.6 • n=7 Participants
|
35.2 kg/m2
STANDARD_DEVIATION 4.3 • n=5 Participants
|
34.5 kg/m2
STANDARD_DEVIATION 4.2 • n=4 Participants
|
|
Total body fat
|
36 percentage
STANDARD_DEVIATION 5 • n=5 Participants
|
37 percentage
STANDARD_DEVIATION 6 • n=7 Participants
|
38 percentage
STANDARD_DEVIATION 6 • n=5 Participants
|
37 percentage
STANDARD_DEVIATION 6 • n=4 Participants
|
|
Fasting plasma glucose
|
153 mg/dl
STANDARD_DEVIATION 37 • n=5 Participants
|
158 mg/dl
STANDARD_DEVIATION 41 • n=7 Participants
|
144 mg/dl
STANDARD_DEVIATION 43 • n=5 Participants
|
152 mg/dl
STANDARD_DEVIATION 44 • n=4 Participants
|
|
Hemoglobin A1c
|
7.2 percentage
STANDARD_DEVIATION 1.2 • n=5 Participants
|
7.5 percentage
STANDARD_DEVIATION 1.3 • n=7 Participants
|
7.3 percentage
STANDARD_DEVIATION 1.1 • n=5 Participants
|
7.3 percentage
STANDARD_DEVIATION 1.2 • n=4 Participants
|
|
Use of glucose-lowering medications
Metformin
|
27 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
|
Use of glucose-lowering medications
Sulfonylurea
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Use of glucose-lowering medications
Insulin
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
|
Fasting plasma insulin
|
18 uU/mL
STANDARD_DEVIATION 13 • n=5 Participants
|
22 uU/mL
STANDARD_DEVIATION 14 • n=7 Participants
|
16 uU/mL
STANDARD_DEVIATION 10 • n=5 Participants
|
18 uU/mL
STANDARD_DEVIATION 13 • n=4 Participants
|
|
Fasting free fatty acids
|
0.41 umol/ml
STANDARD_DEVIATION 0.15 • n=5 Participants
|
0.39 umol/ml
STANDARD_DEVIATION 0.14 • n=7 Participants
|
0.41 umol/ml
STANDARD_DEVIATION 0.15 • n=5 Participants
|
0.40 umol/ml
STANDARD_DEVIATION 0.14 • n=4 Participants
|
|
Intrahepatic triglyceride content
|
10.5 percentage
STANDARD_DEVIATION 5.8 • n=5 Participants
|
11.7 percentage
STANDARD_DEVIATION 5.7 • n=7 Participants
|
13.8 percentage
STANDARD_DEVIATION 8.4 • n=5 Participants
|
12.2 percentage
STANDARD_DEVIATION 7.0 • n=4 Participants
|
|
Plasma AST
|
40 U/L
STANDARD_DEVIATION 23 • n=5 Participants
|
41 U/L
STANDARD_DEVIATION 22 • n=7 Participants
|
32 U/L
STANDARD_DEVIATION 18 • n=5 Participants
|
37 U/L
STANDARD_DEVIATION 21 • n=4 Participants
|
|
Plasma ALT
|
53 U/L
STANDARD_DEVIATION 33 • n=5 Participants
|
53 U/L
STANDARD_DEVIATION 32 • n=7 Participants
|
40 U/L
STANDARD_DEVIATION 25 • n=5 Participants
|
49 U/L
STANDARD_DEVIATION 31 • n=4 Participants
|
|
Total cholesterol
|
171 mg/dl
STANDARD_DEVIATION 40 • n=5 Participants
|
174 mg/dl
STANDARD_DEVIATION 44 • n=7 Participants
|
170 mg/dl
STANDARD_DEVIATION 53 • n=5 Participants
|
172 mg/dl
STANDARD_DEVIATION 46 • n=4 Participants
|
|
LDL-cholesterol
|
94 mg/dl
STANDARD_DEVIATION 33 • n=5 Participants
|
98 mg/dl
STANDARD_DEVIATION 39 • n=7 Participants
|
91 mg/dl
STANDARD_DEVIATION 44 • n=5 Participants
|
94 mg/dl
STANDARD_DEVIATION 39 • n=4 Participants
|
|
HDL-cholesterol
|
39 mg/dl
STANDARD_DEVIATION 10 • n=5 Participants
|
39 mg/dl
STANDARD_DEVIATION 9 • n=7 Participants
|
38 mg/dl
STANDARD_DEVIATION 10 • n=5 Participants
|
38 mg/dl
STANDARD_DEVIATION 9 • n=4 Participants
|
|
Triglycerides
|
154 mg/dl
n=5 Participants
|
156 mg/dl
n=7 Participants
|
163 mg/dl
n=5 Participants
|
158 mg/dl
n=4 Participants
|
|
Statin use
|
25 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
80 Participants
n=4 Participants
|
|
NAFLD activity score
|
4.2 units on a scale
STANDARD_DEVIATION 1.6 • n=5 Participants
|
3.9 units on a scale
STANDARD_DEVIATION 1.6 • n=7 Participants
|
3.7 units on a scale
STANDARD_DEVIATION 1.3 • n=5 Participants
|
4.0 units on a scale
STANDARD_DEVIATION 1.5 • n=4 Participants
|
|
Steatosis
|
1.8 units on a scale
STANDARD_DEVIATION 0.7 • n=5 Participants
|
1.7 units on a scale
STANDARD_DEVIATION 0.8 • n=7 Participants
|
1.6 units on a scale
STANDARD_DEVIATION 0.8 • n=5 Participants
|
1.7 units on a scale
STANDARD_DEVIATION 0.7 • n=4 Participants
|
|
Inflammation
|
1.6 units on a scale
STANDARD_DEVIATION 0.6 • n=5 Participants
|
1.3 units on a scale
STANDARD_DEVIATION 0.5 • n=7 Participants
|
1.4 units on a scale
STANDARD_DEVIATION 0.5 • n=5 Participants
|
1.4 units on a scale
STANDARD_DEVIATION 0.6 • n=4 Participants
|
|
Hepatocyte ballooning
|
0.9 units on a scale
STANDARD_DEVIATION 0.8 • n=5 Participants
|
0.9 units on a scale
STANDARD_DEVIATION 0.8 • n=7 Participants
|
0.7 units on a scale
STANDARD_DEVIATION 0.6 • n=5 Participants
|
0.8 units on a scale
STANDARD_DEVIATION 0.7 • n=4 Participants
|
|
Fibrosis
|
1.5 units on a scale
STANDARD_DEVIATION 1.0 • n=5 Participants
|
1.6 units on a scale
STANDARD_DEVIATION 1.2 • n=7 Participants
|
1.4 units on a scale
STANDARD_DEVIATION 1.1 • n=5 Participants
|
1.5 units on a scale
STANDARD_DEVIATION 1.1 • n=4 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Number of patients with reduction of at least 2 points in the nonalcoholic fatty liver disease activity score (NAS) (with reduction in at least 2 different histological categories) without worsening of fibrosis. NAS is the sum of the separate scores for steatosis (0-3), hepatocellular ballooning (0-2) and lobular inflammation (0-3), and ranges from 0-8 . The scoring system is based on the following grading: Steatosis: 0 = \<5%; 1 = 5-33%; 2 = \>33-66%; 3 = \>66%. Lobular Inflammation: 0 = No foci 1 = \<2 foci/200x; 2 = 2-4 foci/200x, 3 = \>4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis.
Outcome measures
| Measure |
Placebo
n=32 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Liver Histology (Kleiner's et al Criteria, Hepatology 2005)
|
7 Participants
|
13 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: Month 18Population: Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Resolution of NASH was defined as absence of NASH after 18 months of therapy in patients with definite NASH (presence of zone 3 accentuation of macrovesicular steatosis of any grade, hepatocellular ballooning of any degree, and lobular inflammatory infiltrates of any amount) at baseline.
Outcome measures
| Measure |
Placebo
n=32 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Number of Participants With Resolution of NASH Without Worsening of Fibrosis
|
5 Participants
|
14 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: Month 18Population: Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Mean change in individual scores compared to baseline. Steatosis range 0-3, where: 0 = \<5% fat; 1 = 5-33% fat; 2 = \>33-66% fat; 3 = \>66% fat. Lobular Inflammation, range 0-3, where: 0 = No foci 1 = \<2 foci/200x; 2 = 2-4 foci/200x, 3 = \>4 foci/200x. Hepatocyte Ballooning, range 0-2, where: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis stage, range 0-4, where: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis.
Outcome measures
| Measure |
Placebo
n=32 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Mean Individual Histological Scores
Steatosis
|
-0.4 units on a scale
Standard Deviation 0.9
|
-1.0 units on a scale
Standard Deviation 1.0
|
-1.3 units on a scale
Standard Deviation 1.0
|
|
Mean Individual Histological Scores
Inflammation
|
-0.2 units on a scale
Standard Deviation 0.8
|
-0.4 units on a scale
Standard Deviation 0.7
|
-0.6 units on a scale
Standard Deviation 0.7
|
|
Mean Individual Histological Scores
Ballooning
|
-0.1 units on a scale
Standard Deviation 0.9
|
-0.5 units on a scale
Standard Deviation 0.9
|
-0.6 units on a scale
Standard Deviation 0.9
|
|
Mean Individual Histological Scores
Fibrosis
|
-0.3 units on a scale
Standard Deviation 1.1
|
-0.6 units on a scale
Standard Deviation 1.0
|
-0.6 units on a scale
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: Month 18Population: Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Number of patients with improvement of at least 1 grade in each of the histological parameters. Steatosis: 0 = \<5%; 1 = 5-33%; 2 = \>33-66%; 3 = \>66%. Lobular Inflammation: 0 = No foci 1 = \<2 foci/200x; 2 = 2-4 foci/200x, 3 = \>4 foci/200x. Hepatocyte Ballooning: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning. Fibrosis: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis.
Outcome measures
| Measure |
Placebo
n=32 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Individual Histological Scores
Steatosis
|
15 Participants
|
24 Participants
|
32 Participants
|
|
Individual Histological Scores
Inflammation
|
14 Participants
|
13 Participants
|
25 Participants
|
|
Individual Histological Scores
Ballooning
|
11 Participants
|
18 Participants
|
23 Participants
|
|
Individual Histological Scores
Fibrosis
|
10 Participants
|
19 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of therapy
Change from baseline in intrahepatic triglyceride content after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Liver Fat by Magnetic Resonance Imaging and Spectroscopy (MRS).
|
1 percentage
Standard Deviation 7
|
-6 percentage
Standard Deviation 6
|
-10 percentage
Standard Deviation 6
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up
Change from baseline in weight
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Weight
|
-0.8 kg
Standard Deviation 4.2
|
0.5 kg
Standard Deviation 5.6
|
5.7 kg
Standard Deviation 5.4
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up.
Weight (in kg) / (Height \[in m\] x Height \[in m\])
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Body Mass Index
|
-0.6 kg/m2
Standard Deviation 1.6
|
0.1 kg/m2
Standard Deviation 2.3
|
1.4 kg/m2
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up
Change from baseline in total body fat by DEX after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Total Body Fat by DEXA
|
0 percentage
Standard Deviation 3
|
0 percentage
Standard Deviation 3
|
2 percentage
Standard Deviation 3
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up
Change from baseline in plasma AST after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Plasma AST
|
-8 U/L
Standard Deviation 28
|
-15 U/L
Standard Deviation 20
|
-10 U/L
Standard Deviation 10
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up
Change from baseline in plasma ALT after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Plasma ALT
|
-6 U/L
Standard Deviation 42
|
-24 U/L
Standard Deviation 29
|
-18 U/L
Standard Deviation 17
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of therapy
Change from baseline after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Fasting Plasma Glucose
|
6 mg/dl
Standard Deviation 53
|
-3 mg/dl
Standard Deviation 39
|
-16 mg/dl
Standard Deviation 36
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up, not on insulin therapy
Change from baseline after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=16 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=18 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=19 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Fasting Plasma Insulin
|
3 uU/ml
Standard Deviation 12
|
-3 uU/ml
Standard Deviation 6
|
-3 uU/ml
Standard Deviation 6
|
SECONDARY outcome
Timeframe: Month 18Population: Patients completing 18 months of follow-up, not on insulin therapy
This is a method for assessing insulin resistance (IR) based on measurements of glucose and insulin during the oral glucose tolerance test. The formula used is = (10000/(SQRT(fasting plasma glucose \* fasting plasma insulin \* ((fasting plasma glucose \* 15 + glucose at minute 30 \* 30 + glucose at minute 60 \* 30 + glucose at minute 90 \* 30 + glucose at minute 120 \* 15)/120)\*((fasting plasma insulin \* 15 + insulin at minute 30 \* 30 + insulin at minute 60 \* 30 + insulin at minute 90 \* 30 + insulin at minute 120 \* 15)/120))), with a lower value representing worse insulin resistance.
Outcome measures
| Measure |
Placebo
n=16 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=18 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=19 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Matsuda Index
|
2.53 units on a scale
Standard Error 0.39
|
2.31 units on a scale
Standard Error 0.29
|
4.02 units on a scale
Standard Error 0.72
|
SECONDARY outcome
Timeframe: Month 18Change from baseline in plasma total cholesterol after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Total Cholesterol
|
-11 mg/dl
Standard Deviation 31
|
5 mg/dl
Standard Deviation 29
|
1 mg/dl
Standard Deviation 43
|
SECONDARY outcome
Timeframe: Month 18Population: All patients completing 18 months of follow-up
Change from baseline in plasma triglycerides after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Triglycerides
|
13 mg/dl
Interval -2.0 to 46.0
|
14 mg/dl
Interval -28.0 to 74.0
|
-2 mg/dl
Interval -48.0 to 31.0
|
SECONDARY outcome
Timeframe: Month 18Population: All patients completing 18 months of follow-up
Change from baseline in plasma HDL-cholesterol after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
HDL-cholesterol
|
-1 mg/dl
Standard Deviation 4
|
1 mg/dl
Standard Deviation 4
|
3 mg/dl
Standard Deviation 7
|
SECONDARY outcome
Timeframe: Month 18Population: All patients completing 18 months of therapy
Change from baseline in plasma LDL-cholesterol after 18 months of therapy
Outcome measures
| Measure |
Placebo
n=24 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=33 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=29 Participants
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
LDL-cholesterol
|
-12 mg/dl
Standard Deviation 31
|
0 mg/dl
Standard Deviation 30
|
-4 mg/dl
Standard Deviation 31
|
Adverse Events
Placebo
Serious events: 5 serious events
Other events: 15 other events
Deaths: 0 deaths
Vitamin E
Serious events: 6 serious events
Other events: 18 other events
Deaths: 2 deaths
Pioglitazone + Vitamin E
Serious events: 12 serious events
Other events: 23 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Placebo
n=32 participants at risk
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 participants at risk
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 participants at risk
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Cardiac disorders
Arrhythmia
|
3.1%
1/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Cardiac disorders
Hypertensive crisis
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Gastrointestinal disorders
Pancreatitis
|
3.1%
1/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Gastrointestinal disorders
Diverticulitis
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Endocrine disorders
Hypertriglyceridemia
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Infections and infestations
Tonsillar abscess
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Cardiac disorders
Endocarditis
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Nervous system disorders
Subdural hematoma
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Gastrointestinal disorders
Biopsy-related complications
|
6.2%
2/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
5.4%
2/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Musculoskeletal and connective tissue disorders
Back, joint, or hernia repair surgery
|
3.1%
1/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Renal and urinary disorders
Diagnosis of prostate cancer
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.7%
1/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma/COPD exacerbation
|
0.00%
0/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
5.4%
2/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
Other adverse events
| Measure |
Placebo
n=32 participants at risk
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E-placebo: Placebo of vitamin E will be given to arm 1.
|
Vitamin E
n=36 participants at risk
Patients with T2DM and biopsy-proven NASH.
Pioglitazone-placebo: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Depending on randomization, subjects adjudicated to placebo will be started at the same time as the active (pioglitazone) arm and following the same up-titration. Placebo pills have the same characteristics as pills with active medication.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
Pioglitazone + Vitamin E
n=37 participants at risk
Patients with T2DM and biopsy-proven NASH.
Pioglitazone: This is a RCT in which all patients will be educated on a -500 kcal/day diet and a healthy lifestyle. Pioglitazone will be started on 30 mg/day, titrated to the maximal dose (45 mg/day) at two months and continued at this dose for the rest of the clinical trial.
Vitamin E: All participants will receive vitamin E 400 IU orally twice daily.
|
|---|---|---|---|
|
Cardiac disorders
Atypical chest pain or epigastralgia
|
9.4%
3/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
11.1%
4/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
16.2%
6/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Cardiac disorders
Lower limb edema
|
3.1%
1/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
13.5%
5/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Gastrointestinal disorders
Diarrhea/constipation
|
18.8%
6/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
16.7%
6/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
10.8%
4/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Hepatobiliary disorders
AST/ALT elevations
|
9.4%
3/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
2.8%
1/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection, sinusitis, bronchitis
|
18.8%
6/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
13.9%
5/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
8.1%
3/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Respiratory, thoracic and mediastinal disorders
Unspecific dyspnea
|
6.2%
2/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
11.1%
4/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
18.9%
7/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Endocrine disorders
Hypoglycemia
|
18.8%
6/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
19.4%
7/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
35.1%
13/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Musculoskeletal and connective tissue disorders
Bone fractures
|
6.2%
2/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
11.1%
4/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
0.00%
0/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
|
Musculoskeletal and connective tissue disorders
Back or joint pain
|
12.5%
4/32 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
16.7%
6/36 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
24.3%
9/37 • Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
|
Additional Information
Dr. Kenneth Cusi
Malcom Randall VA Medical Center
Phone: 352-273-8662
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place