The Role of TLR4 on Lipid-induced Insulin Resistance

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

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.

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

Details

• Lead Sponsor: The University of Texas Health Science Center at San Antonio
• Treatments: Insulin; Insulin, Globin Zinc

Criteria

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.