Status:

TERMINATED

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

Lead Sponsor:

The University of Texas Health Science Center at San Antonio

Conditions:

Insulin Sensitivity

Eligibility:

All Genders

18-65 years

Phase:

PHASE2

Brief 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...

Detailed Description

E5564 = Eritoran

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

January 1 2015

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 1 2018

Estimated Enrollment :

15 Patients enrolled

Trial Details

Trial ID

NCT02267317

Start Date

January 1 2015

End Date

September 1 2018

Last Update

March 4 2020

Active Locations (1)

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Audie L. Murphy VA Hospital, STVHCS

San Antonio, Texas, United States, 78229