Pilot Study to Evaluate the Effect of Fasting on the NLRP3 Inflammasome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Determine whether the NLRP3 inflammasome is blunted by a 24 hours fast in PBMC's from normal volunteers.
研究概览
简要总结
Background:
- Restricting calories can help a person reduce risk factors for heart disease. Researchers have found that not eating or drinking anything but water for 24 hours prevents the activation of a component of the immune system, called the inflammasome. The inflammasome is associated with the development of diabetes and heart disease. Researchers want to learn more about the body s response to fasting.
Objective:
- To explore the benefits of calorie restriction on heart health.
Eligibility:
- Healthy adults ages 21 32 with a body mass index between 26 and 29.
Design:
- Participants will be screened with a medical history, physical exam and blood test.
- Participants will not eat or drink after 10 p.m. before their first visit.
- Participants have breakfast at the clinic. The breakfast will be about 500 calories. Then they will not eat or drink (except water) for 24 hours.
- Participants will return to the clinic the next morning. They will have blood drawn. Then they will have breakfast. Blood will be drawn again at 1 hour and 3 hours after the meal.
- Blood and urine tests at the end of the fast and following the meals will be done to confirm that participants have fasted for the full 24-hour period.
详细描述
A caloric restricted diet has numerous health effects including the reduction in numerous cardiovascular disease risk factors. The cellular programs activated by caloric restriction are similarly turned on in preclinical studies in response to a 24-hour fast. We have found that a beneficial effect of a 24-hour fasting blunts the activation of a component of the immune system, termed the inflammasome, which is associated with the development of diabetes and atherosclerosis. We would like to study the inflammasome in human blood cells to evaluate whether the beneficial immune effects of fasting/caloric restriction are operational in humans. Blood samples to test the immune response will be collected in subjects after a fixed caloric meal and in response to a 24-hour fast (water intake will not be restricted). The objective of this pilot study is to identify if these immune adaptive pathways can be activated in human subjects as a possible readout to test whether this pathway could be investigated as a therapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases such as diabetes and/or atherosclerosis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 37 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Determine whether the NLRP3 inflammasome is blunted by a 24 hours fast in PBMC's from normal volunteers.
时间窗: 24 hours
The primary outcome will be the change in IL-1 secretion in response to inflammasome stimulation in PBMC s comparing the fasted response to the fed response. As there are two fed responses, we will initially determine whether inflammasome induction differs between the peak post- prandial insulin effect (1 hr) and the peak post-prandial fatty acid levels (3 hr). The higher mean IL-1 levels between the two fed states will be considered the index fed response and will be compared to the fasting levels as the primary outcome. The comparisons will be performed using paired two-tailed Student t-tests. Significance will be tested at the 0.05 alpha level in this pilot study.
次要结局
- Evaluate whether these effects are associated with activation of the Sirt3 and its canonical mitochondrial adaptive programs.(end of study)
- Determine whether serum from subjects in fasted state will blunt the inflammasome compared to serum from the fed stat in a human transformed macrophage cell line.(end of study)