The Role of TLR4 on Lipid-induced Insulin Resistance (Eritoran1)

The University of Texas System (UT)

Status and phase: Completed; Phase 2

Conditions: Insulin Sensitivity

Treatments: Drug: Eritoran; Drug: D5W (5% Dextrose in water)

Study type: Interventional

Funder types: Other

Identifiers

NCT02321111

HSC20140497H

Details and patient eligibility

About

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.

Full description

E5564 = Eritoran

Enrollment: 10 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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10 participants in 3 patient groups

D5W (5% Dextrose in water) + Saline

Active Comparator group

Description:

IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours plus Saline infusion at a rate of 30 mL/hour

Treatment:

Drug: D5W (5% Dextrose in water)

D5W (5% Dextrose in water) + Intralipid

Active Comparator group

Description:

IV Administration of 5% Dextrose in water /D5W (vehicle) 12 mg plus Intralipid infusion at a rate of 30 ml/hour

Treatment:

Drug: D5W (5% Dextrose in water)

Eritoran + Intralipid

Active Comparator group

Description:

IV administration of Eritoran 12 mg every 12 hours plus Intralipid infusion at a rate of 30 ml/hour

Treatment:

Drug: Eritoran