The Effects of Oral Dipyridamole Treatment on the Innate Immune Response During Human Endotoxemia.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Circulating cytokines
研究概览
简要总结
During sepsis and septic shock the immune response can be overwhelming leading to excessive tissue damage, organ failure and death. Ideally, the inflammatory response is modulated leading to both adequate protection to invading pathogens as well as limitation of an exuberant immune response. In the last few years adenosine is proposed to have a central role in the modulation of inflammation. In unfavorable conditions such as hypoxia, ischemia or inflammation adenosine is quickly up-regulated; with concentrations up to tenfold in septic patients. Many animal studies have shown that adenosine is able to attenuate the inflammatory response and decrease mortality rates. Therefore, pharmacological elevation of the adenosine concentration is an potential target to attenuate inflammation and limit organ injury. Dipyridamole, an adenosine re-uptake inhibitor is able to increase the adenosine concentration and limit ischemia-reperfusion injury. In order to study the effects of dipyridamole on the inflammatory response we aim to use the so called human endotoxemia model. This model permits elucidation of key players in the immune response to a gram negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 and ≤ 35 years
排除标准
- •Use of any medication.
- •History of allergic reaction to dipyridamole
- •Bleeding disorder.
- •Previous spontaneous vagal collapse.
- •History, signs or symptoms of cardiovascular disease.
- •Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block.
- •Hypertension (defined as RR systolic > 160 or RR diastolic > 90).
- •Hypotension (defined as RR systolic < 100 or RR diastolic < 50).
- •Renal impairment (defined as plasma creatinin >120 μmol/l).
- •Liver enzyme abnormalities or positive hepatitis serology.
- •Positive HIV serology or any other obvious disease associated with immune deficiency.
- •Febrile illness in the week before the LPS challenge.
- •Participation in another drug trial or donation of blood 3 months prior to the planned LPS challenge.
研究组 & 干预措施
Endotoxemia placebo
Endotoxin combined with placebo
干预措施: Placebo (Drug)
Endotoxemia placebo
Endotoxin combined with placebo
干预措施: LPS (Other)
Endotoxemia Dipyridamole
Endotoxin combined with Dipyridamol treatment
干预措施: Dipyridamole (Drug)
Endotoxemia Dipyridamole
Endotoxin combined with Dipyridamol treatment
干预措施: LPS (Other)
结局指标
主要结局
Circulating cytokines
时间窗: 24 hours after LPS administration
TNFx, IL6, IL10, IL1RA
次要结局
- Hemodynamics(24 hours after LPS administration)
- Sensitivity to norepinephrine(24 hrs after LPS administration)
- Additional blood samples will be drawn for genetic testing and measurement of: mRNA and proteins part of the adenosine metabolism(24 hours after LPS administration)
- Oxydative stress(24 hours after LPS administration)
- Endothelial-dependent and independent vasorelaxation(24 hours after LPS administration)
- Markers of endothelial damage and circulating endothelial cells(24 hrs after LPS administration)
- Urinary excretion of markers of renal injury(24 hrs after LPS administration)
- Adenosine and related nucleotide concentrations(24 hrs after LPS administration)