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Systemic Inflammatory Response to CCRE (Endoscreen)

2019年9月18日 更新者:University of North Carolina, Chapel Hill

Systemic Inflammatory Response to 20,000 EU Clinical Center Reference Endotoxin in Normal Adults

Purpose: The purpose of this study is to classify volunteers as endotoxin-responders or non-responders following inhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE). Endotoxin is a commonly encountered bioaerosol and component of indoor and outdoor air pollution. For reasons that remain unclear, some individuals appear to be more susceptible to the inflammatory effects of inhaled endotoxin than are others, possibly owing to single nucleotide polymorphisms in the Toll-like receptor 4 (TLR4) gene that influence TLR4 signaling and function. These susceptible individuals represent a population of particular interest for further mechanistic studies of the effects of endotoxin and for therapeutic trials. Susceptibility to inhaled endotoxin will be determined by measuring change in peripheral blood neutrophil counts, a biomarker of systemic inflammation, following inhaled CCRE. In our previous work, the investigators have found that inhalation of 20,000 EU CCRE is well tolerated and induces measurable increase in neutrophil content of peripheral blood in susceptible individuals. Our hope is that this CCRE inhalation protocol can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin.

研究概览

地位

完全的

条件

干预/治疗

详细说明

This is a single center, screening study involving recruitment of 18 normal volunteers (NV). The protocol is powered to compare absolute neutrophil count (ANC) in the blood 6 hours after inhalational challenge with CCRE compared baseline. In addition, as secondary endpoints, the investigators will evaluate inflammatory cytokine levels in systemic circulation and access for the presence of genes thought to be related to endotoxin response. Visits will be conducted by a study coordinator or other study staff, physical exams will be performed by the PI or other study physician.

Eighteen subjects will be recruited. There will be no gender or ethnic restrictions, and subjects will be healthy volunteers. Prior to enrollment in this study, subjects will have participated in our protocol 98-0799 (screening and database study for the CEMALB). Data such as medical history and allergy skin testing collected during the screening protocol will be included with data in this study. Subjects with positive allergy skin testing will not be excluded. Spirometry will be performed to determine the current level of lung function.

In order to identify those individuals who appear more susceptible to the systemic inflammatory effects of endotoxin exposure, subjects will undergo inhaled endotoxin challenge at the baseline visit followed 6 hours later by blood draw for complete blood count with differential to allow for calculation of absolute neutrophil count (ANC). Subjects will be considered "responders" if their peripheral ANC increases by at least 20% following inhaled endotoxin challenge.

研究类型

介入性

注册 (实际的)

25

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • North Carolina
      • Chapel Hill、North Carolina、美国、27599
        • Environmental Protection Agency Human Studies facility

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 50年 (成人)

接受健康志愿者

是的

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Subjects must be 18-50 years of age to be eligible for study participation
  2. Subjects must be willing to and able to provide informed consent and participate in all study procedures
  3. Normal lung function, defined as (Knudson 1976/1984 predicted set):

    • 1. Forced Vital Capacity (FVC) of > 80% of that predicted for gender, ethnicity, age and height
    • 2. Forced Expiratory Volume in the first second (FEV1) of > 80% of that predicted for gender, ethnicity, age and height
    • 3. FEV1/FVC ratio of > 0.75 of that predicted for gender, ethnicity, age and height
  4. Oxygen saturation of > 94% Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
  5. Symptom Score (defined in section "f") no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.

Exclusion Criteria:

  1. Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.
  2. Physician directed emergency treatment for asthma exacerbation within the preceding 3 months.
  3. Moderate or Severe asthma
  4. Exacerbation of asthma more than 2x/week that would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
  5. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
  6. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
  7. History of intubation for asthma
  8. Daily use of NSAIDs, or inability to withhold NSAIDs for 4 days prior to dosing.
  9. Use of medications that may impact the results of the study to include, but not limited to, systemic corticosteroids, beta blockers.
  10. Cigarette smoking > 1 pack per month.
  11. BMI>35.
  12. Pregnant or breast feeding women will not be included.
  13. Subjects who are employed within the past 6 months in an occupation with high risk for endotoxin exposure, such as grain storage sites or swine containment.
  14. Subjects will be deferred after any acute, non-chronic medical condition requiring treatment, such as bronchitis, pneumonia or febrile illness for a minimum of 4 weeks after complete resolution of symptoms.

    -

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:其他
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:CCRE
20,000 EU of CCRE (Clinical Center Reference Endotoxin)
Endotoxin challenge: Subjects will undergo inhalation of 20,000 EU CCRE. The CCRE will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes).
其他名称:
  • endotoxin, lipopolysaccharide (LPS)

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Change in peripheral blood PMNs
大体时间:6 hrs post exposure
The objective of this study is to identify endotoxin responders, characterized by an increase in post-CCRE peripheral blood polymorphonuclear (PMN)s compared to that day's baseline values of > 20%. Thus, there will be two data points for this cohort, blood PMNs at baseline and PMNs 6 hours following 20,000 endotoxin units (EU) of CCRE.
6 hrs post exposure

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Michelle Hernandez, MD、UNC

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2017年12月11日

初级完成 (实际的)

2019年8月6日

研究完成 (实际的)

2019年8月6日

研究注册日期

首次提交

2016年7月25日

首先提交符合 QC 标准的

2016年7月25日

首次发布 (估计)

2016年7月28日

研究记录更新

最后更新发布 (实际的)

2019年9月20日

上次提交的符合 QC 标准的更新

2019年9月18日

最后验证

2019年9月1日

更多信息

与本研究相关的术语

关键字

其他研究编号

  • 15-1458

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

IPD 计划说明

for internal analysis only

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

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