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

• Status: Terminated
• Trial end date: 2018-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Nicolas Musi; The University of Texas Health Science Center at San Antonio
• Treatments: Insulin

Criteria

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.