Phase 2 Study of The Role of Pharmacologic Inhibition of TLR4 With E5564 on Glucose Metabolism in Insulin Resistant Subjects.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Effect of Eritoran on Hepatic Insulin Sensitivity
研究概览
简要总结
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.
详细描述
E5564 = Eritoran
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participant, Care Provider, Investigator, Outcomes Assessor
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Obese Group-D5W
Obese subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours
干预措施: D5W (Drug)
Obese Group - Eritoran
Obese subjects receive IV administration of Eritoran 12 mg every 12 hours
干预措施: Eritoran (Drug)
Diabetes (T2DM) Group - D5W
T2DM subjects receive IV administration of 5% Dextrose in water/D5W (vehicle) 12 mg every 12 hours
干预措施: D5W (Drug)
Diabetes (T2DM) Group - Eritoran
T2DM subjects receive IV administration of Eritoran 12 mg every 12 hours
干预措施: Eritoran (Drug)
结局指标
主要结局
Effect of Eritoran on Hepatic Insulin Sensitivity
时间窗: 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.
Effect of Eritoran on Muscle Insulin Sensitivity
时间窗: 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.
次要结局
- Effect of Eritoran on TLR4 Expression in Muscle Tissue(72 hours)
- Effect of Eritoran on TLR4 Expresison in Adipose Tissue(72 hours)
- Effect of Eritoran on TLR4 Expression in Peripheral Blood Monocytes(72 hours)
- Effect of Eritoran on Plasma TNF-alpha (Tumor Necrosis Factor-alpha) Concentration(72 hours)
- Effect of Eritoran on Intramyocellular Diacylglycerol and Ceramide Content(72 hours)