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Trial record 13 of 343 for:    hepatic steatosis AND fat AND Nonalcoholic Fatty Liver

The Effect Of NS-0200 Versus Placebo On Hepatic Fat Content In Patients With Non Alcoholic Fatty Liver Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02546609
Recruitment Status : Completed
First Posted : September 11, 2015
Results First Posted : May 2, 2018
Last Update Posted : May 2, 2018
Sponsor:
Information provided by (Responsible Party):
NuSirt Biopharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition NAFLD
Interventions Drug: Leu-Met-Sil 0.5
Drug: Leu-Met-Sil 1.0
Drug: Placebo
Enrollment 91
Recruitment Details Subjects meeting all inclusion criteria and no exclusion criteria were randomized to one of the three treatment arms in the ratio of 1:1:1. Adult males and females (age 18-75) with CT, MRI, biopsy, or ultrasound consistent with NAFLD within the past 6 months.
Pre-assignment Details  
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Period Title: Overall Study
Started 24 35 32
Completed 22 24 25
Not Completed 2 11 7
Reason Not Completed
Withdrawal by Subject             0             1             2
Adverse Event             0             6             1
Protocol Violation             0             1             1
Lost to Follow-up             2             3             1
travel or work schedule restriction             0             0             2
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg Total
Hide Arm/Group Description

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Total of all reporting groups
Overall Number of Baseline Participants 24 34 32 90
Hide Baseline Analysis Population Description
Demographic and other baseline characteristics were analyzed using the ITT Population with subjects who met the inclusion criteria.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 34 participants 32 participants 90 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
24
 100.0%
34
 100.0%
27
  84.4%
85
  94.4%
>=65 years
0
   0.0%
0
   0.0%
5
  15.6%
5
   5.6%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 34 participants 32 participants 90 participants
46.3  (10.42) 45.1  (11.72) 45.9  (12.71) 45.7  (11.64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 34 participants 32 participants 90 participants
Female
12
  50.0%
21
  61.8%
17
  53.1%
50
  55.6%
Male
12
  50.0%
13
  38.2%
15
  46.9%
40
  44.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 34 participants 32 participants 90 participants
Hispanic or Latino
6
  25.0%
12
  35.3%
12
  37.5%
30
  33.3%
Not Hispanic or Latino
18
  75.0%
22
  64.7%
20
  62.5%
60
  66.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 34 participants 32 participants 90 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   3.1%
1
   1.1%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   8.3%
1
   2.9%
0
   0.0%
3
   3.3%
White
21
  87.5%
31
  91.2%
29
  90.6%
81
  90.0%
More than one race
1
   4.2%
1
   2.9%
0
   0.0%
2
   2.2%
Unknown or Not Reported
0
   0.0%
1
   2.9%
2
   6.3%
3
   3.3%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 24 participants 34 participants 32 participants 90 participants
96.83  (15.061) 94.44  (16.332) 94.11  (17.225) 94.96  (16.192)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 24 participants 34 participants 32 participants 90 participants
170.1  (9.48) 169.6  (10.58) 167  (10.75) 168.8  (10.34)
Body mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 24 participants 34 participants 32 participants 90 participants
33.5  (4.534) 32.60  (3.486) 33.52  (4.167) 33.17  (4.008)
Fasting Plasma Glucose  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 24 participants 34 participants 32 participants 90 participants
108.2  (16.53) 104.3  (14.28) 115.4  (27.61) 109.3  (20.86)
HbA1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated hemoglobin
Number Analyzed 24 participants 34 participants 32 participants 90 participants
5.59  (0.495) 5.65  (0.528) 5.86  (0.738) 5.71  (0.609)
Childbearing Potential   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 17 participants 50 participants
Child-bearing potential with adequate birth contro
3
  25.0%
6
  28.6%
3
  17.6%
12
  24.0%
Postmenopausal
1
   8.3%
4
  19.0%
3
  17.6%
8
  16.0%
Surgically Sterile
8
  66.7%
11
  52.4%
11
  64.7%
30
  60.0%
[1]
Measure Analysis Population Description: Childbearing potential is only applicable to the female participants hence the difference in overall population and number analyzed for this category.
1.Primary Outcome
Title Change in Hepatic Fat
Hide Description To evaluate the change in hepatic fat content assessed by proton-density-fat-fraction (PDFF) employing magnetic resonance imaging (MRI).
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean percent change (SD) in hepatic fat content (%) from Baseline to Week 16 (Day 112) for each treatment group was assessed.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 24 24
Mean (Standard Deviation)
Unit of Measure: percentage
-10.046  (17.5335) 3.083  (25.5230) -4.013  (24.6302)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments Analysis of variance (ANOVA) model: with treatment group as the factor. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0572
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments Analysis of variance (ANOVA) model: with treatment group as the factor. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3770
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
2.Secondary Outcome
Title Change in Serum AlanineAaminotransferase (ALT) Levels
Hide Description Serum AlanineAminotransferase (ALT) will be examined through standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in serum ALT levels from Baseline to Week 16 was assessed
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 24 24
Mean (Standard Deviation)
Unit of Measure: U/L
-4.1  (20.09) 1.8  (22.67) -2.7  (22.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3811
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8479
Comments [Not Specified]
Method Mixed Effect Model Repeat Measurement
Comments [Not Specified]
3.Secondary Outcome
Title Change in Circulating Cytokeratin 18 Fragments (M30)
Hide Description Change in Circulating Cytokeratin 18 Fragments (M30) from Baseline to Week 16 will be examined through standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in circulating cytokeratin 18 fragments (M30, U/L) from Baseline to week 16 was assessed
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 24 24
Mean (Standard Deviation)
Unit of Measure: U/L
70.685  (306.3480) 55.386  (273.1235) 37.847  (222.6792)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7742
Comments [Not Specified]
Method Mixed effect Model Repeat Measurement
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6666
Comments [Not Specified]
Method Mixed effect Model Repeat Measurement
Comments [Not Specified]
4.Secondary Outcome
Title Change in Heamoglobin A1c (HbA1c)
Hide Description HbA1c will be examined through standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in HbA1c from Baseline to Week 16 was assessed.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 24 24
Mean (Standard Deviation)
Unit of Measure: percentage
0.07  (0.125) -0.15  (0.287) -0.11  (0.250)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0164
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
5.Secondary Outcome
Title Change in Fasting Glucose
Hide Description Fasting glucose will be examined through standard fasting blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in fasting glucose from Baseline to Week 16 was assessed. The difference in the actual participants analyzed and per protocol population is due to missing or technically erroneous data.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 23 23
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.8  (10.66) -2.7  (11.59) -6.3  (9.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4099
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1455
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
6.Secondary Outcome
Title Change in Insulin
Hide Description Insulin levels will be examined through standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in insulin from Baseline to Week 16 was assessed. The difference in the actual participants analyzed and per protocol population is due to missing or technically erroneous data.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 23 23
Mean (Standard Deviation)
Unit of Measure: μIU/mL
-8.30  (24.38) -6.60  (12.30) -5.30  (15.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2559
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9776
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
7.Secondary Outcome
Title Change in Blood Lipids (Cholesterol)
Hide Description Lipid levels such as cholesterol will be examined by standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in total cholesterol from Baseline to Week 16 was assessed.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 24 24
Mean (Standard Deviation)
Unit of Measure: mg/dL
-0.8  (27.56) -20.5  (28.02) -5.9  (37.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2265
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8366
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
8.Secondary Outcome
Title Change in Blood Lipids (High Density Lipoprotein:HDL)
Hide Description Lipid levels such as HDL will be examined by standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in LDL from Baseline to Week 16 was assessed. The difference in the actual participants analyzed and per protocol population is because HDL could not be calculated for some participants.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 21 22 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
-1.0  (23.81) -13.3  (27.16) 1.2  (42.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3470
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6221
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
9.Secondary Outcome
Title Change in Low Density Lipoproteins (LDL)
Hide Description Lipid levels such as LDL will be examined by standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the mean change (SD) in LDL from Baseline to Week 16 was assessed. The difference in the actual participants analyzed and per protocol population is because LDL could not be calculated for some participants.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 21 22 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
-1.0  (23.81) -13.3  (27.16) 1.2  (42.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3470
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6221
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
10.Secondary Outcome
Title Change in Triglycerides
Hide Description Lipid levels such as triglycerides will be examined by standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean values are presented since the data were skewed. Corresponding arithmetic mean changes from baseline for Treatments A, B and C in the Per Protocol Population were +54.9, -48.9 and -28.0 mg/dL respectively. This accounts for the p-value of p=0.0129 for Treatment B.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 22 24 24
Geometric Mean (Standard Error)
Unit of Measure: mg/dL
1.0  (0.06) 0.8  (0.06) 0.9  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0129
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4316
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
11.Secondary Outcome
Title Change in C-reactive Protein
Hide Description CRP levels will be examined by standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the geometric mean change (SE) in C-reactive protein from Baseline to Week 16 was assessed. The difference in the actual participants analyzed and per protocol population is due to missing or technically erroneous data.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 21 24 24
Geometric Mean (Standard Error)
Unit of Measure: mg/L
1.02  (0.129) 1.27  (0.178) 1.08  (0.170)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments [Not Specified]
Type of Statistical Test Other
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Statistical Test of Hypothesis P-Value 0.1946
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4697
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
12.Secondary Outcome
Title Change in Insulin Sensitivity (HOMA-IR)
Hide Description HOMA-IR levels will be examined by standard blood chemistry
Time Frame Baseline, Day 112
Hide Outcome Measure Data
Hide Analysis Population Description
For the Per-Protocol Population (N=70), the change in geometric mean (SE) in HOMA-IR from Baseline to Week 16 was assessed. The difference in the actual participants analyzed and per protocol population is due to missing or technically erroneous data.
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description:

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Overall Number of Participants Analyzed 20 22 22
Geometric Mean (Standard Error)
Unit of Measure: mU/L
0.89  (0.076) 0.80  (0.078) 0.85  (0.096)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 0.5mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3474
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Leu Met Sil 1.0mg
Comments MMRM model: with treatment group, visit, and treatment-by-visit interaction as fixed effects, the baseline value of the response variable as a covariate, and subject as a random effect. Placebo is used as the reference group.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8832
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Time Frame 112 days
Adverse Event Reporting Description Treatment-Emergent Adverse Event (TEAE) is defined as an adverse event occurring on or after the first dose of randomized study medication, or existing prior to the time of and worsening after the time of the first dose of randomized study medication.
 
Arm/Group Title Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Hide Arm/Group Description

3 capsules BID containing 99% Avicel PH302 and 1% magnesium stearate (w/w)

Placebo: Placebo

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 0.5 mg of sildenafil.

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

Sildenafil Citrate 0.5 mg: Sildenafil 0.5 mg BID

3 capsules BID consisting of 2 capsules containing 550 mg L-leucine each and 1 capsule containing 500 mg metformin and 1.0 mg of sildenafil.

Sildenafil 1.0 mg: Sildenafil 1.0 mg

Metformin: 500 mg Metformin BID

Leucine: 1100 mg Leucine BID

All-Cause Mortality
Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)      0/34 (0.00%)      0/32 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/24 (0.00%)      1/34 (2.94%)      1/32 (3.13%)    
Gastrointestinal disorders       
Appendicitis   0/24 (0.00%)  0 0/34 (0.00%)  0 1/32 (3.13%)  1
Gastritis erosive   0/24 (0.00%)  0 1/34 (2.94%)  1 0/32 (0.00%)  0
Ileus   0/24 (0.00%)  0 1/34 (2.94%)  1 0/32 (0.00%)  0
Vomiting   0/24 (0.00%)  0 1/34 (2.94%)  1 0/32 (0.00%)  0
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 Leu Met Sil 0.5mg Leu Met Sil 1.0mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/24 (75.00%)      25/34 (73.53%)      26/32 (81.25%)    
Endocrine disorders       
Type 2 Diabetes mellitus   0/24 (0.00%)  0 1/34 (2.94%)  1 2/32 (6.25%)  2
Eye disorders       
Vision Blurred   0/24 (0.00%)  0 2/34 (5.88%)  2 0/32 (0.00%)  0
Vision blurred   0/24 (0.00%)  0 2/34 (5.88%)  2 1/32 (3.13%)  1
Gastrointestinal disorders       
Abdominal pain   0/24 (0.00%)  0 3/34 (8.82%)  3 1/32 (3.13%)  1
Constipation   0/24 (0.00%)  0 2/34 (5.88%)  2 1/32 (3.13%)  1
Diarrhoea   2/24 (8.33%)  2 15/34 (44.12%)  15 12/32 (37.50%)  12
Dyspepsia   4/24 (16.67%)  4 3/34 (8.82%)  3 2/32 (6.25%)  2
Flatulence   1/24 (4.17%)  1 3/34 (8.82%)  3 4/32 (12.50%)  4
Gastrooesophageal reflux disease   0/24 (0.00%)  0 0/34 (0.00%)  0 2/32 (6.25%)  2
Vomiting   1/24 (4.17%)  1 5/34 (14.71%)  5 2/32 (6.25%)  2
General disorders       
Headache   2/24 (8.33%)  2 5/34 (14.71%)  5 1/32 (3.13%)  1
Nausea   3/24 (12.50%)  3 6/34 (17.65%)  6 5/32 (15.63%)  5
Hepatobiliary disorders       
Blood triglycerides increase   0/24 (0.00%)  0 0/34 (0.00%)  0 2/32 (6.25%)  2
Musculoskeletal and connective tissue disorders       
Arthralgia   0/24 (0.00%)  0 2/34 (5.88%)  2 1/32 (3.13%)  1
Back pain   1/24 (4.17%)  1 0/34 (0.00%)  0 3/32 (9.38%)  3
Nervous system disorders       
Dizziness   0/24 (0.00%)  0 1/34 (2.94%)  1 4/32 (12.50%)  4
Respiratory, thoracic and mediastinal disorders       
Cough   2/24 (8.33%)  2 0/34 (0.00%)  0 1/32 (3.13%)  1
Upper respiratory tract infection   1/24 (4.17%)  1 2/34 (5.88%)  2 1/32 (3.13%)  1
Skin and subcutaneous tissue disorders       
Dermatitis Contact   0/24 (0.00%)  0 2/34 (5.88%)  2 0/32 (0.00%)  0
Social circumstances       
Fatigue   1/24 (4.17%)  1 2/34 (5.88%)  2 1/32 (3.13%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Barbara Cannon
Organization: Nusirt Biopharma Inc.
Phone: 615-656-7898
Responsible Party: NuSirt Biopharma
ClinicalTrials.gov Identifier: NCT02546609     History of Changes
Other Study ID Numbers: NS-0200-01
First Submitted: September 3, 2015
First Posted: September 11, 2015
Results First Submitted: February 26, 2018
Results First Posted: May 2, 2018
Last Update Posted: May 2, 2018