Mechanism of Microbiome-induced Insulin Resistance in Humans (Aim2)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Insulin Sensitivity
研究概览
简要总结
The purpose of this study is to determine whether microbiome modulation and an experimental reduction in plasma LPS concentration improve inflammation and insulin action in insulin resistant (obese and T2DM) subjects.
详细描述
In this Aim we will test the hypothesis that lowering lipopolysaccharide (LPS) concentration in the circulation will improve systemic (muscle) inflammation and glucose metabolism in insulin resistant (obese and T2DM) subjects by protecting the intestinal barrier with a synbiotic (Bifidobacterium longum R0175 and oligofructose) or by sequestering LPS in the gastrointestinal lumen with sevelamer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Both genders (50%, male). All races and 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.
- •Hematocrit (HCT)≥ 34%, serum creatinine ≤ 1.4 mg/dl, and normal results of serum electrolytes, urinalysis, and coagulation tests. Liver function tests (LFTs) up to 2 times normal
- •Stable body weight (±2%) for ≥ 3 months.
- •Two 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. If the subject has been on a stable dose for the past 3 months, the following agents will be permitted: calcium channel blockers, β-blockers, ACE inhibitors, angiotensin receptor blockers, and statins
- •History of allergy to sevelamer.
- •Non-steroidal anti-inflammatory drugs or systemic steroid use for more than a 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 biopsy in accordance with the primary physician.
- •Use of agents that affect gut flora (e.g. antibiotics, colestyramine, lactulose, PEG) within 3 months.
- •History of heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the ECG), peripheral vascular disease, pulmonary disease, smokers.
- •Poorly controlled blood pressure (systolic BP>170, diastolic BP>95 mmHg).
- •Active inflammatory, autoimmune, hepatic, gastrointestinal, malignant, and psychiatric disease.
- •History of gastrointestinal surgery or gastrointestinal obstruction within two years.
研究组 & 干预措施
Type2 Diabetes Mellitus - Placebo
Type 2 Diabetes Mellitus subjects will receive maltodextrin (placebo)
干预措施: Maltodextrin (Drug)
Obese with NGT - Placebo
Obese (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) subjects will receive maltodextrin (placebo)
干预措施: Maltodextrin (Drug)
Lean with NGT -Placebo
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive maltodextrin (placebo)
干预措施: Maltodextrin (Drug)
Type2 Diabetes Mellitus - Synbiotic
Type 2 Diabetic subjects will receive synbiotic
干预措施: Synbiotic (Drug)
Type2 Diabetes Mellitus - Sevelamer
Type 2 Diabetic subjects will receive sevelamer
干预措施: Sevelamer (Drug)
Obese with NGT - Synbiotic
Obese (BMI = 30-37 kg/m2) normal glucose tolerant subjects (NGT) will receive Synbiotic
干预措施: Synbiotic (Drug)
Obese with NGT - Sevelamer
Obese subjects (BMI = 30-37 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
干预措施: Sevelamer (Drug)
Lean with NGT - Synbiotic
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Synbiotic
干预措施: Synbiotic (Drug)
Lean with NGT - Sevelamer
Lean (BMI< 26 kg/m2) normal glucose tolerant (NGT) will receive Sevelamer
干预措施: Sevelamer (Drug)
结局指标
主要结局
Insulin Sensitivity
时间窗: Change from baseline insulin sensitivity at 28 days of the intervention.
Insulin sensitivity in skeletal muscle (M value) as measured by hyperinsulinemic euglycemic clamp study. The clamp study tests the ability of peripheral tissues such as skeletal muscle to uptake glucose in response to a constant insulin stimulus, which give a measure of sensitivity to insulin action. 60 mU/m2\*min insulin was infused into subjects for 180 minutes with concomitant adjustment of glucose infusion rate using D20 glucose to maintain a clamped plasma glucose concentration of 100 mg/dL. When the glucose infusion rate equals the rate of glucose uptake and the targeted glucose concentration is achieved, the clamp is at steady-state equilibrium. Steady-state glucose infusion rate at 150min-180mins was used as the measure to calculate the M value.
次要结局
- Plasma Endotoxin Level and Its Panel.(Change from baseline plasma endotoxin level and its panel during 28 days.)
- Gut Permeability(Change from baseline gut permeability at 24 days of the intervention.)