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Completed

NCT Number: NCT02321111

The Role of TLR4 on Lipid-induced Insulin Resistance

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.

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Key information

Conditions

Insulin Sensitivity Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Audie L. Murphy VA Hospital, STVHCS

San Antonio, Texas, 78229, United States

About this study

E5564 = Eritoran

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Eritoran

Drug

Eritoran = E5564 Eritoran is a pharmacologic inhibitor of TLR4.

Other names: E5564

D5W (5% Dextrose in water)

Drug

D5W = 5% Dextrose Water Vehicle

Other names: Vehicle

Primary outcomes

  1. Effect of Eritoran on Muscle Insulin Sensitivity

    Time frame: 72 hours

    Muscle insulin sensitivity = muscle insulin sensitivity is determined by euglycemic hyperinsulinemic clamp procedure. M value (mg glucose / kg of body weight / minute) calculated from the clamp is measured. Higher M value indicates better insulin sensitivity. There is no established reference range.

  2. Effect of Eritoran on Hepatic Insulin Sensitivity

    Time frame: 72 hours

    Hepatic insulin sensitivity = is determined by euglycemic hyperinsulinemic clamp procedure. Endogenous glucose production or EGP (mg/kg/min) calculated from the clamp is measured. Lower EGP indicates better hepatic insulin sensitivity. There is no established reference range.

Secondary outcomes

  1. Effect of Eritoran on TLR4 Expression on Peripheral Blood Monocytes

    Time frame: 72 hours

    TLR4 expression on the peripheral blood monocytes is determined by flow cytometry using arbitrary units. Higher TLR4 expression indicates higher inflammatory response. There is no reference range.

  2. Effect of Eritoran on Plasma Cytokine Concentration

    Time frame: 72 hours

    TNF-alpha levels (tumor necrosis factor-alpha) are determined by ELISA. Higher level indicates higher inflammatory response. There is no established reference range.

  3. Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content

    Time frame: 72 hours

    Intramyocellular diacylglycerol and ceramide content are determined by mass spectrometry. Higher levels have been associated with diabetes.

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center at San Antonio

Other

Registry information

Acronym: Eritoran1

Important dates

Study start
2015
Primary completion
2018
Study completion
2018
First posted
Dec 22, 2014
Registry last updated
Oct 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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