The Effect of TLR4 Inhibition in Obese and Type 2 Diabetic Subjects (Eritoran2)

The University of Texas System (UT)

Status and phase: Terminated; Phase 2

Conditions: Insulin Sensitivity

Treatments: Drug: D5W; Drug: Eritoran

Study type: Interventional

Funder types: Other

Identifiers

NCT02267317

HSC20140498H

Details and patient eligibility

About

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.

Full description

E5564 = Eritoran

Enrollment: 15 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) with normal glucose-tolerant subjects without a family history of type 2 DM
• obese (BMI 30-37 kg/m2) with normal glucose-tolerant subjects
• Type 2 DM subjects base on ADA criteria, who have HbA1c <8.5% and control with diet or sulfonylureas.
• 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

• Current treatment with drugs known to affect glucose and lipid homeostasis. Subjects on a stable dose of statin (>3 months) 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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15 participants in 4 patient groups

Obese Group-D5W

Active Comparator group

Description:

Obese subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours

Treatment:

Drug: D5W

Obese Group - Eritoran

Active Comparator group

Description:

Obese subjects receive IV administration of Eritoran 12 mg every 12 hours

Treatment:

Drug: Eritoran

Diabetes (T2DM) Group - D5W

Active Comparator group

Description:

T2DM subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours

Treatment:

Drug: D5W

Diabetes (T2DM) Group - Eritoran

Active Comparator group

Description:

T2DM subjects receive IV administration of Eritoran 12 mg every 12 hours

Treatment:

Drug: Eritoran