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Study drug expired
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To determine whether pharmacologic inhibition of Toll-like receptor 4 (TLR4) with eritoran for injection (E5564) will reduce inflammation and improve glucose metabolism in insulin resistant (obese and T2DM) subjects.
E5564 = Eritoran
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Obese Group-D5W | Active Comparator | Obese subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours |
|
| Obese Group - Eritoran | Active Comparator | Obese subjects receive IV administration of Eritoran 12 mg every 12 hours |
|
| Diabetes (T2DM) Group - D5W | Active Comparator | T2DM subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours |
|
| Diabetes (T2DM) Group - Eritoran | Active Comparator | T2DM subjects receive IV administration of Eritoran 12 mg every 12 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eritoran | Drug | Pharmacologic inhibitor of TLR4 receptors. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Eritoran on Muscle Insulin Sensitivity | 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. | 72 hours |
| Effect of Eritoran on Hepatic Insulin Sensitivity | 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. | 72 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Eritoran on TLR4 Expression in Muscle Tissue | TLR4 expression in muscle tissue is determined by RNAseq using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range. | 72 hours |
| Effect of Eritoran on TLR4 Expresison in Adipose Tissue |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicolas Musi, MD | Audie L. Murphy VA Hospital, STVHCS San Antonio, Texas, United States 78229 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Audie L. Murphy VA Hospital, STVHCS | San Antonio | Texas | 78229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36066991 | Derived | Liang H, Sathavarodom N, Colmenares C, Gelfond J, Espinoza SE, Ganapathy V, Musi N. Effect of acute TLR4 inhibition on insulin resistance in humans. J Clin Invest. 2022 Nov 1;132(21):e162291. doi: 10.1172/JCI162291. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Obese Group - D5W - Eritoran | Obese subjects randomized to receive D5W first, then Eritoran |
| FG001 | Obese Group - Eritoran - D5W | Obese subjects randomized to receive Eritoran first, then D5W. |
| FG002 | Diabetes (T2DM) Group - D5W - Eritoran | T2DM subjects randomized to receive D5W first then Eritoran |
| FG003 | Diabetes (T2DM) Group - Eritoran - D5W | T2DM subjects randomized to receive Eritoran first then D5W |
| FG004 | Lean Group - D5W - Eritoran | Lean subjects randomized to receive D5W first then Eritoran |
| FG005 | Lean Group - Eritoran - D5W | Lean subjects randomized to receive Eritoran first then d5W |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Infusion1 |
| |||||||||||||
| Washout (3-4weeks Between Infusions) |
| |||||||||||||
| Infusion2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Obese Group | Subjects with BMI >30 kg/m2 were enrolled to receive two infusions, the order of which was randomly assigned. |
| BG001 | Type 2 Diabetic Subjects | Subjects with BMI >30 kg/m2 and 2-hour Oral Glucose Tolerance Test >200mg/dL |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Effect of Eritoran on Muscle Insulin Sensitivity | 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. | Data from T2DM subjects and Lean subject were not collected for primary outcome measure because of insufficient number of participants in the 2 groups. | Posted | Mean | Standard Error | mg/kg/min | 72 hours |
|
19 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Obese Group - Placebo | Obese subjects - IV administration of D5W (5% Dextrose in water) |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Phlebitis Grade 1, 2 or 3 | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hanyu Liang | University of Texas Health San Antonio | 210-617-5300 | 15197 | liangh0@uthscsa.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 10, 2016 | Apr 16, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C512420 | eritoran |
| C404742 | E5564 |
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Participant, Care Provider, Investigator, Outcomes Assessor
| D5W | Drug | 5% Dextrose Water = Vehicle |
|
|
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. |
| 72 hours |
| Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes | 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. | 72 hours |
| Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration | TNF-alpha levels are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range. | 72 hours |
| Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content | Intramyocellular diacylglycerol and ceramide content are determined by mass spectrometry. Higher levels have been associated with diabetes. | 72 hours |
| COMPLETED |
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| NOT COMPLETED |
|
|
| COMPLETED |
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| NOT COMPLETED |
|
| BG002 | Lean/Healthy | Subjects with BMI <26 kg/m2 and normal glucose tolerant |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| HbA1c | Mean | Standard Deviation | Percentage of glycated hemoglobin |
|
| Fasting plasma glucose | Mean | Standard Deviation | mg/dL |
|
Obese subjects - IV administration of Eritoran 12 mg every 12 hours
| OG002 | Diabetes (T2DM) Group - Placebo | T2DM subjects - IV administration of D5W (5% Dextrose in water) |
| OG003 | Diabetes (T2DM) Group - Eritoran | T2DM subjects - IV administration of Eritoran 12 mg every 12 hours |
| OG004 | Lean - Placebo | Lean subjects - IV administration of D5W (5% Dextrose in water) |
| OG005 | Lean - Eritoran | Lean subjects - IV administration of Eritoran 12 mg every 12 hours |
|
|
| Primary | Effect of Eritoran on Hepatic Insulin Sensitivity | 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. | Data from T2DM subjects and Lean subject were not collected for primary outcome measure because of insufficient number of participants in the 2 groups. | Posted | Mean | Standard Error | mg/kg/min | 72 hours |
|
|
|
| Secondary | Effect of Eritoran on TLR4 Expression in Muscle Tissue | TLR4 expression in muscle tissue is determined by RNAseq using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range. | 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. | Posted | Mean | Standard Error | AU | 72 hours |
|
|
|
| Secondary | Effect of Eritoran on TLR4 Expresison in Adipose Tissue | 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. | 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. | Posted | Mean | Standard Deviation | AU | 72 hours |
|
|
|
| Secondary | Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes | 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. | Data from T2DM subjects and Lean subject were not analyzed because the number of participants was insufficient in the 2 groups. | Posted | Mean | Standard Error | AU | 72 hours |
|
|
|
| Secondary | Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration | TNF-alpha levels are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range. | Data from T2DM subjects and Lean subject were not analyzed because the number of participants was insufficient in the 2 groups. | Posted | Mean | Standard Error | pg/ml | 72 hours |
|
|
|
| Secondary | Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content | Intramyocellular diacylglycerol and ceramide content are determined by mass spectrometry. Higher levels have been associated with diabetes. | Data were not collected due to lack of funding. | Posted | 72 hours |
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 9 |
| 11 |
| EG001 | Obese Group - Eritoran | Obese subjects - IV administration of Eritoran 12 mg every 12 hours | 0 | 11 | 0 | 11 | 9 | 11 |
| EG002 | Diabetes (T2DM) Group - Placebo | T2DM subjects - IV administration of D5W (5% Dextrose in water) | 0 | 3 | 0 | 3 | 1 | 3 |
| EG003 | Diabetes (T2DM) Group - Eritoran | T2DM subjects - IV administration of Eritoran 12 mg every 12 hours | 0 | 3 | 0 | 3 | 2 | 3 |
| EG004 | Lean/Healthy Group - Placebo | Lean subjects - IV administration of D5W (5% Dextrose in water) | 0 | 1 | 0 | 1 | 0 | 1 |
| EG005 | Lean/Healthy Group - Eritoran | Lean subjects - IV administration of Eritoran 12 mg every 12 hours | 0 | 1 | 0 | 1 | 0 | 1 |
| Dermatology | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Hot flashes | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Hypokalemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
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