The Role of TLR4 on Lipid-induced Insulin Resistance

Insulin Sensitivity Clinical Trial

— Eritoran1  

Official title:

The Role of TLR4 on Lipid-Induced Insulin Resistance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02321111
• Other study ID #: HSC20140497H
• Status: Completed
• Phase: Phase 2
• Start date: January 2015
• Est. completion date: September 2018

Study information

• Verified date: September 2019
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether pharmacologic inhibition of Toll-like receptor 4 (TLR4) with eritoran for injection (E5564) prevents lipid-induced insulin resistance in lean, normal glucose tolerant (NGT) subjects.

Description:

E5564 = Eritoran

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Subjects capable of giving informed consent.

• lean (BMI <26 kg/m2)

• normal glucose-tolerant subjects (completers) without a family history of Type 2 diabetes mellitus (DM)

• Both genders. (50% males)

• Age = 18-65 years. Older subjects are excluded because aging is a pro-inflammatory state.

• All ethnic groups

• Premenopausal women in the follicular phase, non-lactating, and with a negative pregnancy test. Postmenopausal women on stable dose of or not exposed to hormone replacement for >=6 months.

• Lab: Hematocrit >=34%, serum creatinine <=1.4 mg/dL, normal electrolytes, urinalysis, and coagulation tests. Liver function tests up to 2x normal range.

• Stable body weight (+/-1%) for >=3 months.

• One or less sessions of strenuous exercise/wk for last 6 months.

Exclusion Criteria:

• Presence of diabetes or impaired glucose tolerance based on ADA criteria;

• Current treatment with drugs known to affect glucose and lipid homeostasis. Subjects on a stable dose of statin (>3months) are eligible.

• Non-steroidal anti-inflammatory drugs or systemic steroid use for more than 1 week within 3 months.

• Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsies.

• History of heart disease (New York Heart Classification greater than class II; more than non-specific ST-T wave changes on the ECG), peripheral vascular disease, pulmonary disease, smokers.

• Poorly controlled blood pressure (systolic BP>160, diastolic BP>90 mmHg).

• Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and psychiatric disease.

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity

Intervention

Drug:
• Eritoran
Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.
• D5W (5% Dextrose in water)
D5W = 5% Dextrose Water Vehicle

Locations

Country	Name	City	State
United States	Audie L. Murphy VA Hospital, STVHCS	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	72 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.	72 hours
Secondary	Effect of Eritoran on TLR4 Expression on Peripheral Blood Monocytes	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.	72 hours
Secondary	Effect of Eritoran on Plasma Cytokine Concentration	TNF-alpha levels (tumor necrosis factor-alpha) are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range.	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.	72 hours