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Prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) in Hispanics With Diabetes Mellitus Type 2 (T2DM) and Role of Treatment (VA NASH)

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ClinicalTrials.gov Identifier: NCT01002547
Recruitment Status : Completed
First Posted : October 27, 2009
Results First Posted : September 11, 2018
Last Update Posted : September 11, 2018
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Nonalcoholic Steatohepatitis
Interventions Drug: pioglitazone-placebo
Drug: pioglitazone
Dietary Supplement: Vitamin E
Drug: Vitamin E-placebo
Enrollment 105
Recruitment Details 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).
Pre-assignment Details 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).
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description

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.

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.

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.

Period Title: Overall Study
Started 32 36 37
Completed 24 33 29
Not Completed 8 3 8
Reason Not Completed
Withdrawal by Subject             4             0             5
Lost to Follow-up             2             1             1
Physician Decision             1             0             0
Death             0             2             2
Adverse Event             1             0             0
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E Total
Hide Arm/Group Description

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.

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.

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 of all reporting groups
Overall Number of Baseline Participants 32 36 37 105
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 36 participants 37 participants 105 participants
57  (11) 60  (9) 60  (6) 59  (9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 36 participants 37 participants 105 participants
Female
2
   6.3%
3
   8.3%
7
  18.9%
12
  11.4%
Male
30
  93.8%
33
  91.7%
30
  81.1%
93
  88.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 36 participants 37 participants 105 participants
White
23
  71.9%
27
  75.0%
26
  70.3%
76
  72.4%
African American
2
   6.3%
4
  11.1%
3
   8.1%
9
   8.6%
Hispanic
7
  21.9%
5
  13.9%
8
  21.6%
20
  19.0%
Body mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 32 participants 36 participants 37 participants 105 participants
33.6  (4.0) 33.8  (4.6) 35.2  (4.3) 34.5  (4.2)
Total body fat  
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 32 participants 36 participants 37 participants 105 participants
36  (5) 37  (6) 38  (6) 37  (6)
Fasting plasma glucose  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 32 participants 36 participants 37 participants 105 participants
153  (37) 158  (41) 144  (43) 152  (44)
Hemoglobin A1c  
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 32 participants 36 participants 37 participants 105 participants
7.2  (1.2) 7.5  (1.3) 7.3  (1.1) 7.3  (1.2)
Use of glucose-lowering medications  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 36 participants 37 participants 105 participants
Metformin
27
  84.4%
29
  80.6%
29
  78.4%
85
  81.0%
Sulfonylurea
13
  40.6%
15
  41.7%
14
  37.8%
42
  40.0%
Insulin
8
  25.0%
10
  27.8%
10
  27.0%
28
  26.7%
Fasting plasma insulin  
Mean (Standard Deviation)
Unit of measure:  uU/mL
Number Analyzed 32 participants 36 participants 37 participants 105 participants
18  (13) 22  (14) 16  (10) 18  (13)
Fasting free fatty acids  
Mean (Standard Deviation)
Unit of measure:  Umol/ml
Number Analyzed 32 participants 36 participants 37 participants 105 participants
0.41  (0.15) 0.39  (0.14) 0.41  (0.15) 0.40  (0.14)
Intrahepatic triglyceride content  
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 32 participants 36 participants 37 participants 105 participants
10.5  (5.8) 11.7  (5.7) 13.8  (8.4) 12.2  (7.0)
Plasma AST  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 32 participants 36 participants 37 participants 105 participants
40  (23) 41  (22) 32  (18) 37  (21)
Plasma ALT  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 32 participants 36 participants 37 participants 105 participants
53  (33) 53  (32) 40  (25) 49  (31)
Total cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 32 participants 36 participants 37 participants 105 participants
171  (40) 174  (44) 170  (53) 172  (46)
LDL-cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 32 participants 36 participants 37 participants 105 participants
94  (33) 98  (39) 91  (44) 94  (39)
HDL-cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 32 participants 36 participants 37 participants 105 participants
39  (10) 39  (9) 38  (10) 38  (9)
Triglycerides  
Median (Inter-Quartile Range)
Unit of measure:  Mg/dl
Number Analyzed 32 participants 36 participants 37 participants 105 participants
154
(117 to 255)
156
(126 to 210)
163
(108 to 274)
158
(116 to 243)
Statin use  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 36 participants 37 participants 105 participants
25
  78.1%
26
  72.2%
29
  78.4%
80
  76.2%
NAFLD activity score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 32 participants 36 participants 37 participants 105 participants
4.2  (1.6) 3.9  (1.6) 3.7  (1.3) 4.0  (1.5)
[1]
Measure Description:

Calculated as the sum of steatosis grade (0 to 3), inflammation grade (0 to 3), and ballooning grade (0 to 2). Therefore, this score ranges from 0 to 8.

Steatosis: 0 = <5% fat; 1 = 5-33% fat; 2 = >33-66% fat; 3 = >66% fat.

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 stage: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis.

Steatosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 32 participants 36 participants 37 participants 105 participants
1.8  (0.7) 1.7  (0.8) 1.6  (0.8) 1.7  (0.7)
[1]
Measure Description: Steatosis range 0-3, where: 0 = <5% fat; 1 = 5-33% fat; 2 = >33-66% fat; 3 = >66% fat.
Inflammation   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 32 participants 36 participants 37 participants 105 participants
1.6  (0.6) 1.3  (0.5) 1.4  (0.5) 1.4  (0.6)
[1]
Measure Description: Lobular Inflammation, range 0-3, where: 0 = No foci 1 = <2 foci/200x; 2 = 2-4 foci/200x, 3 = >4 foci/200x.
Hepatocyte ballooning   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 32 participants 36 participants 37 participants 105 participants
0.9  (0.8) 0.9  (0.8) 0.7  (0.6) 0.8  (0.7)
[1]
Measure Description: Hepatocyte Ballooning, range 0-2, where: 0 = None; 1 = Few balloon cells; 2 = Many cells/prominent ballooning.
Fibrosis   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 32 participants 36 participants 37 participants 105 participants
1.5  (1.0) 1.6  (1.2) 1.4  (1.1) 1.5  (1.1)
[1]
Measure Description: Fibrosis stage, range 0-4, where: 0 = None; 1 = Perisinusoidal or periportal; 2 = Perisinusoidal and portal/periportal; 3 = Bridging fibrosis, 4 = Cirrhosis.
1.Primary Outcome
Title Liver Histology (Kleiner's et al Criteria, Hepatology 2005)
Hide Description

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.

Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 32 36 37
Measure Type: Count of Participants
Unit of Measure: Participants
7
  21.9%
13
  36.1%
24
  64.9%
2.Secondary Outcome
Title Number of Participants With Resolution of NASH Without Worsening of Fibrosis
Hide Description 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.
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 32 36 37
Measure Type: Count of Participants
Unit of Measure: Participants
5
  15.6%
14
  38.9%
20
  54.1%
3.Secondary Outcome
Title Mean Individual Histological Scores
Hide Description

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.

Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 32 36 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Steatosis -0.4  (0.9) -1.0  (1.0) -1.3  (1.0)
Inflammation -0.2  (0.8) -0.4  (0.7) -0.6  (0.7)
Ballooning -0.1  (0.9) -0.5  (0.9) -0.6  (0.9)
Fibrosis -0.3  (1.1) -0.6  (1.0) -0.6  (0.9)
4.Secondary Outcome
Title Individual Histological Scores
Hide Description

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.

Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Multiple imputation was used to impute missing histologic data for patients who did not complete 18 months of therapy.
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 32 36 37
Measure Type: Count of Participants
Unit of Measure: Participants
Steatosis
15
  46.9%
24
  66.7%
32
  86.5%
Inflammation
14
  43.8%
13
  36.1%
25
  67.6%
Ballooning
11
  34.4%
18
  50.0%
23
  62.2%
Fibrosis
10
  31.3%
19
  52.8%
19
  51.4%
5.Secondary Outcome
Title Liver Fat by Magnetic Resonance Imaging and Spectroscopy (MRS).
Hide Description Change from baseline in intrahepatic triglyceride content after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of therapy
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: percentage
1  (7) -6  (6) -10  (6)
6.Secondary Outcome
Title Weight
Hide Description Change from baseline in weight
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: kg
-0.8  (4.2) 0.5  (5.6) 5.7  (5.4)
7.Secondary Outcome
Title Body Mass Index
Hide Description Weight (in kg) / (Height [in m] x Height [in m])
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up.
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: kg/m2
-0.6  (1.6) 0.1  (2.3) 1.4  (1.6)
8.Secondary Outcome
Title Total Body Fat by DEXA
Hide Description Change from baseline in total body fat by DEX after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: percentage
0  (3) 0  (3) 2  (3)
9.Secondary Outcome
Title Plasma AST
Hide Description Change from baseline in plasma AST after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: U/L
-8  (28) -15  (20) -10  (10)
10.Secondary Outcome
Title Plasma ALT
Hide Description Change from baseline in plasma ALT after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: U/L
-6  (42) -24  (29) -18  (17)
11.Secondary Outcome
Title Fasting Plasma Glucose
Hide Description Change from baseline after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of therapy
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: mg/dl
6  (53) -3  (39) -16  (36)
12.Secondary Outcome
Title Fasting Plasma Insulin
Hide Description Change from baseline after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up, not on insulin therapy
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 16 18 19
Mean (Standard Deviation)
Unit of Measure: uU/ml
3  (12) -3  (6) -3  (6)
13.Secondary Outcome
Title Matsuda Index
Hide Description 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.
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients completing 18 months of follow-up, not on insulin therapy
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 16 18 19
Mean (Standard Error)
Unit of Measure: units on a scale
2.53  (0.39) 2.31  (0.29) 4.02  (0.72)
14.Secondary Outcome
Title Total Cholesterol
Hide Description Change from baseline in plasma total cholesterol after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: mg/dl
-11  (31) 5  (29) 1  (43)
15.Secondary Outcome
Title Triglycerides
Hide Description Change from baseline in plasma triglycerides after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients completing 18 months of follow-up
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Median (Inter-Quartile Range)
Unit of Measure: mg/dl
13
(-2 to 46)
14
(-28 to 74)
-2
(-48 to 31)
16.Secondary Outcome
Title HDL-cholesterol
Hide Description Change from baseline in plasma HDL-cholesterol after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients completing 18 months of follow-up
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: mg/dl
-1  (4) 1  (4) 3  (7)
17.Secondary Outcome
Title LDL-cholesterol
Hide Description Change from baseline in plasma LDL-cholesterol after 18 months of therapy
Time Frame Month 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients completing 18 months of therapy
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description:

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.

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.

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 Number of Participants Analyzed 24 33 29
Mean (Standard Deviation)
Unit of Measure: mg/dl
-12  (31) 0  (30) -4  (31)
Time Frame Adverse events are reported for the entire period of the randomized controlled trial (18 months).
Adverse Event Reporting Description Specific questionnaire focused on weight changes, peripheral edema, fractures, and GI disturbances.
 
Arm/Group Title Placebo Vitamin E Pioglitazone + Vitamin E
Hide Arm/Group Description

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.

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.

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.

All-Cause Mortality
Placebo Vitamin E Pioglitazone + Vitamin E
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/32 (0.00%)   2/36 (5.56%)   2/37 (5.41%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Vitamin E Pioglitazone + Vitamin E
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/32 (15.63%)   6/36 (16.67%)   12/37 (32.43%) 
Cardiac disorders       
Arrhythmia *  1/32 (3.13%)  1/36 (2.78%)  1/37 (2.70%) 
Hypertensive crisis *  0/32 (0.00%)  0/36 (0.00%)  1/37 (2.70%) 
Endocarditis *  0/32 (0.00%)  1/36 (2.78%)  0/37 (0.00%) 
Endocrine disorders       
Hypertriglyceridemia   0/32 (0.00%)  0/36 (0.00%)  1/37 (2.70%) 
Gastrointestinal disorders       
Pancreatitis *  1/32 (3.13%)  0/36 (0.00%)  0/37 (0.00%) 
Diverticulitis *  0/32 (0.00%)  0/36 (0.00%)  1/37 (2.70%) 
Biopsy-related complications   2/32 (6.25%)  1/36 (2.78%)  2/37 (5.41%) 
Infections and infestations       
Tonsillar abscess *  0/32 (0.00%)  0/36 (0.00%)  1/37 (2.70%) 
Cellulitis *  0/32 (0.00%)  1/36 (2.78%)  0/37 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back, joint, or hernia repair surgery *  1/32 (3.13%)  1/36 (2.78%)  1/37 (2.70%) 
Nervous system disorders       
Subdural hematoma *  0/32 (0.00%)  1/36 (2.78%)  0/37 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis *  0/32 (0.00%)  1/36 (2.78%)  0/37 (0.00%) 
Diagnosis of prostate cancer *  0/32 (0.00%)  0/36 (0.00%)  1/37 (2.70%) 
Respiratory, thoracic and mediastinal disorders       
Pneumonia *  0/32 (0.00%)  0/36 (0.00%)  1/37 (2.70%) 
Asthma/COPD exacerbation *  0/32 (0.00%)  1/36 (2.78%)  2/37 (5.41%) 
*
Indicates events were collected by non-systematic assessment
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%
Placebo Vitamin E Pioglitazone + Vitamin E
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/32 (46.88%)   18/36 (50.00%)   23/37 (62.16%) 
Cardiac disorders       
Atypical chest pain or epigastralgia *  3/32 (9.38%)  4/36 (11.11%)  6/37 (16.22%) 
Lower limb edema   1/32 (3.13%)  0/36 (0.00%)  5/37 (13.51%) 
Endocrine disorders       
Hypoglycemia   6/32 (18.75%)  7/36 (19.44%)  13/37 (35.14%) 
Gastrointestinal disorders       
Diarrhea/constipation   6/32 (18.75%)  6/36 (16.67%)  4/37 (10.81%) 
Hepatobiliary disorders       
AST/ALT elevations   3/32 (9.38%)  1/36 (2.78%)  0/37 (0.00%) 
Musculoskeletal and connective tissue disorders       
Bone fractures   2/32 (6.25%)  4/36 (11.11%)  0/37 (0.00%) 
Back or joint pain *  4/32 (12.50%)  6/36 (16.67%)  9/37 (24.32%) 
Respiratory, thoracic and mediastinal disorders       
Upper respiratory infection, sinusitis, bronchitis *  6/32 (18.75%)  5/36 (13.89%)  3/37 (8.11%) 
Unspecific dyspnea   2/32 (6.25%)  4/36 (11.11%)  7/37 (18.92%) 
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
Relative small sample size. A larger sample size could have resulted in significantly positive results for vitamin E alone in secondary outcomes. Because of this we acknowledge that vitamin E may still be an alternative for some patients.
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. Kenneth Cusi
Organization: Malcom Randall VA Medical Center
Phone: 352-273-8662
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT01002547     History of Changes
Other Study ID Numbers: CLIN-015-08F
HSC20090401H ( Other Identifier: IRB UTHSCSA )
VA-ORD#GRANT00508571 ( Other Grant/Funding Number: CSRD CSP )
610-2011 ( Other Identifier: University of Florida IRB-01 )
First Submitted: October 23, 2009
First Posted: October 27, 2009
Results First Submitted: August 13, 2018
Results First Posted: September 11, 2018
Last Update Posted: September 11, 2018