Trial Outcomes & Findings for The Role of TLR4 on Lipid-induced Insulin Resistance (NCT NCT02321111)
NCT ID: NCT02321111
Last Updated: 2019-10-08
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
72 hours
Results posted on
2019-10-08
Participant Flow
Participant milestones
| Measure |
Eritoran/Lipid Then D5W/Saline Then D5W/Lipid
Subjects randomized to receive Eritoran/Lipid first then D5W/Saline then D5W/Lipid
|
D5W/Saline Then D5W/Lipid Then Eritoran/Lipid
Subjects randomized to receive D5W/Saline first then D5W/Lipid then Eritoran/Lipid
|
D5W/Lipid Then D5W/Saline Then Eritoran/Lipid
Subjects randomized to receive D5W/Lipid first then D5W/Saline then Eritoran/Lipid
|
D5W/Lipid Then Eritoran/Lipid Then D5W/Saline
Subjects randomized to receive first D5W/Lipid then Eritoran/Lipid then D5W/Saline
|
Eritoran/Lipid Then D5W/Lipid Then D5W/Saline
Subjects randomized to receive Eritoran/Lipid then D5W/Lipid then D5W/Saline
|
D5W/Saline Then Eritoran/Lipid Then D5W/Lipid
Subjects randomized to receive D5W/Saline then Eritoran/Lipid then D5W/Lipid
|
|---|---|---|---|---|---|---|
|
Infusion1
STARTED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Infusion1
COMPLETED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Infusion1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout1 (3-4weeks Between Infusions)
STARTED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Washout1 (3-4weeks Between Infusions)
COMPLETED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Washout1 (3-4weeks Between Infusions)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Infusion2
STARTED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Infusion2
COMPLETED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Infusion2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout2 (3-4weeks Between Infusions)
STARTED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Washout2 (3-4weeks Between Infusions)
COMPLETED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Washout2 (3-4weeks Between Infusions)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Infusion3
STARTED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Infusion3
COMPLETED
|
1
|
4
|
4
|
1
|
0
|
0
|
|
Infusion3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Role of TLR4 on Lipid-induced Insulin Resistance
Baseline characteristics by cohort
| Measure |
Lean Subjects
n=10 Participants
Ten lean subjects were randomized to receive 3 infusions in different order.
|
|---|---|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 1 • n=99 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
BMI
|
23.8 kg/m^2
STANDARD_DEVIATION 2.2 • n=99 Participants
|
|
HbA1c
|
5.5 Percentage of glycated hemoglobin
STANDARD_DEVIATION 0.3 • n=99 Participants
|
|
Fasting plasma glucose
|
5.5 mg/dL
STANDARD_DEVIATION 0.3 • n=99 Participants
|
PRIMARY outcome
Timeframe: 72 hoursMuscle 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 |
D5W (5% Dextrose in Water) + Saline
n=10 Participants
IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
D5W (5% Dextrose in Water) + Intralipid
n=10 Participants
IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
Eritoran + Intralipid
n=10 Participants
IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour
Eritoran: Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
|
|---|---|---|---|
|
Effect of Eritoran on Muscle Insulin Sensitivity
|
11.9 mg/kg/min
Standard Error 0.6
|
10.2 mg/kg/min
Standard Error 0.7
|
9.8 mg/kg/min
Standard Error 0.6
|
PRIMARY outcome
Timeframe: 72 hoursHepatic 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 |
D5W (5% Dextrose in Water) + Saline
n=10 Participants
IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
D5W (5% Dextrose in Water) + Intralipid
n=10 Participants
IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
Eritoran + Intralipid
n=10 Participants
IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour
Eritoran: Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
|
|---|---|---|---|
|
Effect of Eritoran on Hepatic Insulin Sensitivity
|
2.2 mg/kg/min
Standard Error 0.1
|
2.3 mg/kg/min
Standard Error 0.1
|
2.2 mg/kg/min
Standard Error 0.0
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: Data from 1 subject were not collected due to instrument failure. Therefore, data from 9 subjects were reported.
TLR4 expression on 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 |
D5W (5% Dextrose in Water) + Saline
n=9 Participants
IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
D5W (5% Dextrose in Water) + Intralipid
n=9 Participants
IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
Eritoran + Intralipid
n=9 Participants
IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour
Eritoran: Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
|
|---|---|---|---|
|
Effect of Eritoran on TLR4 Expression on Peripheral Blood Monocytes
|
1.1 AU
Standard Error 0.1
|
1.2 AU
Standard Error 0.2
|
1.1 AU
Standard Error 0.1
|
SECONDARY outcome
Timeframe: 72 hoursTNF-alpha levels (tumor necrosis factor-alpha) are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range.
Outcome measures
| Measure |
D5W (5% Dextrose in Water) + Saline
n=9 Participants
IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
D5W (5% Dextrose in Water) + Intralipid
n=9 Participants
IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
Eritoran + Intralipid
n=9 Participants
IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour
Eritoran: Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
|
|---|---|---|---|
|
Effect of Eritoran on Plasma Cytokine Concentration
|
1.6 pg/ml
Standard Error 0.2
|
2.0 pg/ml
Standard Error 0.3
|
2.0 pg/ml
Standard Error 0.1
|
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
D5W (5% Dextrose in Water) + Saline
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
D5W (5% Dextrose in Water) + Intralipid
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Eritoran + Intralipid
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
D5W (5% Dextrose in Water) + Saline
n=10 participants at risk
IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
D5W (5% Dextrose in Water) + Intralipid
n=10 participants at risk
IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour
D5W (5% Dextrose in water): D5W = 5% Dextrose Water Vehicle
|
Eritoran + Intralipid
n=10 participants at risk
IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour
Eritoran: Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
|
|---|---|---|---|
|
Vascular disorders
Phlebitis Grade 1, 2, or 3
|
60.0%
6/10 • Baseline to 20 months
|
80.0%
8/10 • Baseline to 20 months
|
100.0%
10/10 • Baseline to 20 months
|
|
Skin and subcutaneous tissue disorders
Bruising
|
10.0%
1/10 • Baseline to 20 months
|
0.00%
0/10 • Baseline to 20 months
|
0.00%
0/10 • Baseline to 20 months
|
|
Blood and lymphatic system disorders
Hypokalemia
|
10.0%
1/10 • Baseline to 20 months
|
0.00%
0/10 • Baseline to 20 months
|
0.00%
0/10 • Baseline to 20 months
|
|
Musculoskeletal and connective tissue disorders
Pain
|
10.0%
1/10 • Baseline to 20 months
|
10.0%
1/10 • Baseline to 20 months
|
40.0%
4/10 • Baseline to 20 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/10 • Baseline to 20 months
|
10.0%
1/10 • Baseline to 20 months
|
10.0%
1/10 • Baseline to 20 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory illness
|
0.00%
0/10 • Baseline to 20 months
|
10.0%
1/10 • Baseline to 20 months
|
10.0%
1/10 • Baseline to 20 months
|
Additional Information
Laurie Che Kelly
University of Texas Health San Antonio
Phone: 210-617-5300
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place