Trial Outcomes & Findings for The Effect of TLR4 Inhibition in Obese and Type 2 Diabetic Subjects (NCT NCT02267317)
NCT ID: NCT02267317
Last Updated: 2020-03-04
Results Overview
Muscle insulin sensitivity = muscle insulin sensitivity is determined by euglycemic hyperinsulinemic clamp procedure. M value (mg glucose / kg of body weight / minute) calculated from the clamp is measured. Higher M value indicates better insulin sensitivity. There is no established reference range.
TERMINATED
PHASE2
15 participants
72 hours
2020-03-04
Participant Flow
Participant milestones
| Measure |
Obese Group - D5W - Eritoran
Obese subjects randomized to receive D5W first, then Eritoran
|
Obese Group - Eritoran - D5W
Obese subjects randomized to receive Eritoran first, then D5W.
|
Diabetes (T2DM) Group - D5W - Eritoran
T2DM subjects randomized to receive D5W first then Eritoran
|
Diabetes (T2DM) Group - Eritoran - D5W
T2DM subjects randomized to receive Eritoran first then D5W
|
Lean Group - D5W - Eritoran
Lean subjects randomized to receive D5W first then Eritoran
|
Lean Group - Eritoran - D5W
Lean subjects randomized to receive Eritoran first then d5W
|
|---|---|---|---|---|---|---|
|
Infusion1
STARTED
|
8
|
3
|
1
|
2
|
0
|
1
|
|
Infusion1
COMPLETED
|
8
|
3
|
1
|
2
|
0
|
1
|
|
Infusion1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout (3-4weeks Between Infusions)
STARTED
|
8
|
3
|
1
|
2
|
0
|
1
|
|
Washout (3-4weeks Between Infusions)
COMPLETED
|
6
|
3
|
1
|
2
|
0
|
1
|
|
Washout (3-4weeks Between Infusions)
NOT COMPLETED
|
2
|
0
|
0
|
0
|
0
|
0
|
|
Infusion2
STARTED
|
6
|
3
|
1
|
2
|
0
|
1
|
|
Infusion2
COMPLETED
|
6
|
3
|
1
|
2
|
0
|
1
|
|
Infusion2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Obese Group - D5W - Eritoran
Obese subjects randomized to receive D5W first, then Eritoran
|
Obese Group - Eritoran - D5W
Obese subjects randomized to receive Eritoran first, then D5W.
|
Diabetes (T2DM) Group - D5W - Eritoran
T2DM subjects randomized to receive D5W first then Eritoran
|
Diabetes (T2DM) Group - Eritoran - D5W
T2DM subjects randomized to receive Eritoran first then D5W
|
Lean Group - D5W - Eritoran
Lean subjects randomized to receive D5W first then Eritoran
|
Lean Group - Eritoran - D5W
Lean subjects randomized to receive Eritoran first then d5W
|
|---|---|---|---|---|---|---|
|
Washout (3-4weeks Between Infusions)
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Washout (3-4weeks Between Infusions)
Lost to Follow-up
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
The Effect of TLR4 Inhibition in Obese and Type 2 Diabetic Subjects
Baseline characteristics by cohort
| Measure |
Obese Group
n=11 Participants
Subjects with BMI \>30 kg/m2 were enrolled to receive two infusions, the order of which was randomly assigned.
|
Type 2 Diabetic Subjects
n=3 Participants
Subjects with BMI \>30 kg/m2 and 2-hour Oral Glucose Tolerance Test \>200mg/dL
|
Lean/Healthy
n=1 Participants
Subjects with BMI \<26 kg/m2 and normal glucose tolerant
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58 years
STANDARD_DEVIATION 6.0 • n=99 Participants
|
55 years
STANDARD_DEVIATION 15.6 • n=107 Participants
|
19 years
STANDARD_DEVIATION 0 • n=206 Participants
|
53 years
STANDARD_DEVIATION 12.4 • n=7 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
|
BMI
|
32.1 kg/m^2
STANDARD_DEVIATION 1.8 • n=99 Participants
|
33.5 kg/m^2
STANDARD_DEVIATION 3.3 • n=107 Participants
|
19 kg/m^2
STANDARD_DEVIATION 0 • n=206 Participants
|
31.5 kg/m^2
STANDARD_DEVIATION 4.0 • n=7 Participants
|
|
HbA1c
|
5.4 Percentage of glycated hemoglobin
STANDARD_DEVIATION 0.2 • n=99 Participants
|
6.3 Percentage of glycated hemoglobin
STANDARD_DEVIATION 0.7 • n=107 Participants
|
5.3 Percentage of glycated hemoglobin
STANDARD_DEVIATION 0 • n=206 Participants
|
5.6 Percentage of glycated hemoglobin
STANDARD_DEVIATION 0.5 • n=7 Participants
|
|
Fasting plasma glucose
|
5.1 mg/dL
STANDARD_DEVIATION 0.8 • n=99 Participants
|
6.9 mg/dL
STANDARD_DEVIATION 0.7 • n=107 Participants
|
4.5 mg/dL
STANDARD_DEVIATION 0 • n=206 Participants
|
5.4 mg/dL
STANDARD_DEVIATION 0.9 • n=7 Participants
|
PRIMARY outcome
Timeframe: 72 hoursPopulation: Data from T2DM subjects and Lean subject were not collected for primary outcome measure because of insufficient number of participants in the 2 groups.
Muscle insulin sensitivity = muscle insulin sensitivity is determined by euglycemic hyperinsulinemic clamp procedure. M value (mg glucose / kg of body weight / minute) calculated from the clamp is measured. Higher M value indicates better insulin sensitivity. There is no established reference range.
Outcome measures
| Measure |
Obese Group - Placebo
n=9 Participants
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=9 Participants
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean - Placebo
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean - Eritoran
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Effect of Eritoran on Muscle Insulin Sensitivity
|
8.0 mg/kg/min
Standard Error 0.9
|
10.6 mg/kg/min
Standard Error 1.1
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 72 hoursPopulation: Data from T2DM subjects and Lean subject were not collected for primary outcome measure because of insufficient number of participants in the 2 groups.
Hepatic insulin sensitivity = is determined by euglycemic hyperinsulinemic clamp procedure. Endogenous glucose production or EGP (mg/kg/min) calculated from the clamp is measured. Lower EGP indicates better hepatic insulin sensitivity. There is no established reference range.
Outcome measures
| Measure |
Obese Group - Placebo
n=9 Participants
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=9 Participants
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean - Placebo
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean - Eritoran
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Effect of Eritoran on Hepatic Insulin Sensitivity
|
2.0 mg/kg/min
Standard Error 0.2
|
1.9 mg/kg/min
Standard Error 0.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: The total number of obese subjects enrolled is 9. However, we were only able to obtain muscle biopsies from 7 subjects. In addition, data from T2DM subjects and Lean subject were not collected for this secondary outcome measure because of insufficient number of participants in the 2 groups.
TLR4 expression in muscle tissue is determined by RNAseq using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.
Outcome measures
| Measure |
Obese Group - Placebo
n=7 Participants
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=7 Participants
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean - Placebo
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean - Eritoran
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Effect of Eritoran on TLR4 Expression in Muscle Tissue
|
1 AU
Standard Error 0.11
|
1.16 AU
Standard Error 0.16
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: The total number of obese subjects enrolled is 9. However, we were only able to obtain fat biopsies from 4 subjects. In addition, data from T2DM subjects and Lean subject were not analyzed for this secondary outcome measure because of insufficient number of participants in the 2 groups.
TLR4 expression in the adipose tissue is determined by RNAseq using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.
Outcome measures
| Measure |
Obese Group - Placebo
n=4 Participants
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=4 Participants
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean - Placebo
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean - Eritoran
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Effect of Eritoran on TLR4 Expresison in Adipose Tissue
|
1 AU
Standard Deviation 0.11
|
1.22 AU
Standard Deviation 0.07
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Data from T2DM subjects and Lean subject were not analyzed because the number of participants was insufficient in the 2 groups.
TLR4 expression in the peripheral blood monocytes is determined by flow cytometry using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.
Outcome measures
| Measure |
Obese Group - Placebo
n=9 Participants
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=9 Participants
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean - Placebo
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean - Eritoran
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes
|
1.1 AU
Standard Error 0.1
|
1.2 AU
Standard Error 0.1
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Data from T2DM subjects and Lean subject were not analyzed because the number of participants was insufficient in the 2 groups.
TNF-alpha levels are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range.
Outcome measures
| Measure |
Obese Group - Placebo
n=9 Participants
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=9 Participants
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean - Placebo
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean - Eritoran
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration
|
2.4 pg/ml
Standard Error 0.3
|
2.3 pg/ml
Standard Error 0.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Data were not collected due to lack of funding.
Intramyocellular diacylglycerol and ceramide content are determined by mass spectrometry. Higher levels have been associated with diabetes.
Outcome measures
Outcome data not reported
Adverse Events
Obese Group - Placebo
Obese Group - Eritoran
Diabetes (T2DM) Group - Placebo
Diabetes (T2DM) Group - Eritoran
Lean/Healthy Group - Placebo
Lean/Healthy Group - Eritoran
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Obese Group - Placebo
n=11 participants at risk
Obese subjects - IV administration of D5W (5% Dextrose in water)
|
Obese Group - Eritoran
n=11 participants at risk
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
|
Diabetes (T2DM) Group - Placebo
n=3 participants at risk
T2DM subjects - IV administration of D5W (5% Dextrose in water)
|
Diabetes (T2DM) Group - Eritoran
n=3 participants at risk
T2DM subjects - IV administration of Eritoran 12 mg every 12 hours
|
Lean/Healthy Group - Placebo
n=1 participants at risk
Lean subjects - IV administration of D5W (5% Dextrose in water)
|
Lean/Healthy Group - Eritoran
n=1 participants at risk
Lean subjects - IV administration of Eritoran 12 mg every 12 hours
|
|---|---|---|---|---|---|---|
|
Vascular disorders
Phlebitis Grade 1, 2 or 3
|
63.6%
7/11 • 19 months
|
81.8%
9/11 • 19 months
|
33.3%
1/3 • 19 months
|
66.7%
2/3 • 19 months
|
0.00%
0/1 • 19 months
|
0.00%
0/1 • 19 months
|
|
Skin and subcutaneous tissue disorders
Dermatology
|
9.1%
1/11 • 19 months
|
0.00%
0/11 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/1 • 19 months
|
0.00%
0/1 • 19 months
|
|
Reproductive system and breast disorders
Hot flashes
|
0.00%
0/11 • 19 months
|
9.1%
1/11 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/1 • 19 months
|
0.00%
0/1 • 19 months
|
|
Blood and lymphatic system disorders
Hypokalemia
|
9.1%
1/11 • 19 months
|
0.00%
0/11 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/1 • 19 months
|
0.00%
0/1 • 19 months
|
|
Musculoskeletal and connective tissue disorders
Pain
|
27.3%
3/11 • 19 months
|
18.2%
2/11 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/1 • 19 months
|
0.00%
0/1 • 19 months
|
|
Nervous system disorders
Headache
|
36.4%
4/11 • 19 months
|
27.3%
3/11 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/3 • 19 months
|
0.00%
0/1 • 19 months
|
0.00%
0/1 • 19 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place