The Effects of Woodsmoke Exposure on Nasal Immune Responses to Influenza Infection in Normal Human Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 暂停
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Nasal Mucosal secretome (AUC)
研究概览
简要总结
This study will investigate the effects of woodsmoke (WS) exposure on human nasal mucosal immune responses to viral infection. The study tests the hypotheses that WS exposure modifies biomarkers of nasal mucosal immune function, increases in Live Attenuated Influenza Virus (LAIV) -induced nasal symptoms, and reduces mucosal antibody production.
详细描述
This study will investigate the effects of woodsmoke (WS) exposure on human nasal mucosal immune responses to viral infection. The study tests the hypotheses that WS exposure modifies biomarkers of nasal mucosal immune function, increases LAIV-induced nasal symptoms, and reduces mucosal antibody production. Healthy volunteers will be randomized for a 2-hr exposure to WS or placebo (filtered air) and then inoculated with either live attenuated influenza virus (LAIV) or placebo. Nasal mucosal samples, symptoms, and peripheral blood will be collected on days 1,2,3,7, and 21 post-exposure/LAIV and assessed for a) mucosal antiviral responses using targeted and non-targeted analysis of the secretome and tissue-level gene expression; b) symptoms, virus quantity, differential cell count, and virus-specific antibody levels; and c) biomarker signatures associated with infection outcomes using computational modeling tools.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
This is a randomized, double-blinded study so packaging and labeling by IDS is such that both study participants and study personnel (lab techs) will be blinded to the treatment (either LAIV or placebo) given. Due to the smell of the WS it will not be possible to completely blind subjects or coordinators as to exposure. The contractor maintaining the woodsmoke exposure chamber add a small amount of woodsmoke into the chamber to minimize bias. The risk for bias is felt to be minimal because all of the study's primary and most of the secondary outcomes are laboratory assays for which the technicians performing the assays will be blinded as to subject group. Unblinding will occur at the conclusion of the study or earlier if needed for safety purposes and as dictated by the UNC IRB, study sponsor, and DSMB.
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal lung function,
- •oxygen saturation of >94%,
- •normal blood pressure,
- •no respiratory symptoms on history, no abnormalities on exam, normal pulmonary function testing,
- •18-49 Years of age.
排除标准
- •A history of significant chronic illnesses (to include diabetes, autoimmune diseases, immunodeficiency state, known ischemic heart disease, chronic respiratory diseases such as chronic obstructive pulmonary disease or asthma, hypertension)
- •Positive pregnancy test within 48 hours of the time of challenge
- •Use of any inhaled substance (for medical or recreational purposes).
- •Nonsmokers must have been abstinent from smoking for the prior 12 months, having not smoked more than 1 pack over the course of the previous year.
- •History of allergy to eggs
- •Acute, non-chronic, medical conditions, including (but not limited to) pneumonia or bronchitis requiring antibiotics, febrile illnesses, flu-like symptoms must be totally resolved symptomatically for 3 weeks
- •Unspecified illnesses, which in the judgment of the investigator increase the risk associated with the experimental LAIV infection, will be a basis for exclusion.
- •Expected exposure of subject to immunocompromised individuals (who can be infected by LAIV) for the 3 weeks following LAIV inoculation.
- •Use of immunosuppressive drugs within the past 6 months.
- •Previous Woodsmoke exposure <3 weeks, which is considered to an appropriate washout period
研究组 & 干预措施
Wood smoke followed by LAIV
Participants will receive LAIV after a 2 hour wood smoke exposure.
干预措施: LAIV nasal vaccine is chosen as a model viral infection (Biological)
Wood smoke followed by LAIV
Participants will receive LAIV after a 2 hour wood smoke exposure.
干预措施: Wood smoke (Other)
Wood smoke followed by Placebo
Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.
干预措施: Wood smoke (Other)
Wood smoke followed by Placebo
Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.
干预措施: Placebo for LAIV nasal vaccine is chosen as a model viral infection (Biological)
Clean Air followed by LAIV
Participants will receive LAIV after a 2 hour clean air exposure.
干预措施: LAIV nasal vaccine is chosen as a model viral infection (Biological)
Clean Air followed by LAIV
Participants will receive LAIV after a 2 hour clean air exposure.
干预措施: Placebo for Wood Smoke (clean Air Exposure) (Other)
Clean Air followed by Placebo
Participants will receive a LAIV placebo after a 2 hour clean air exposure.
干预措施: Placebo for LAIV nasal vaccine is chosen as a model viral infection (Biological)
Clean Air followed by Placebo
Participants will receive a LAIV placebo after a 2 hour clean air exposure.
干预措施: Placebo for Wood Smoke (clean Air Exposure) (Other)
结局指标
主要结局
Nasal Mucosal secretome (AUC)
时间窗: Day 0 to Day 7
Analysis of the nasal mucosal secretome (secreted factors identified as responsive to WS and/or LAIV). Area under the curve (AUC) will be calculated for each proteomic profile. Descriptive statistics (means and standard deviations) will be computed for outcomes of interest (AUCs), assuming normal distribution as in previous studies.
Gene Expression (AUC)
时间窗: Day 0 to Day 7
Tissue-level gene expression (genes identified as responsive to WS and/or LAIV) and assessed for: tissue-level gene expression and untargeted metabolomic and proteomic profiles. Area under the curve (AUC) will be calculated for each gene profile. Descriptive statistics (means and standard deviations) will be computed for outcomes of interest (AUCs), assuming normal distribution as in previous studies.
Virus Quantity (AUC)
时间窗: Day 0 to Day 7
Virus quantity in nasal secretions
Nasal Neutrophils (AUC)
时间窗: Day 0 to Day 7
nasal secretion
Nasal Viral Antibodies (AUC)
时间窗: Day 0 to Day 7
virus-specific antibody levels in nasal secretions
Blood Viral Antibodies (AUC)
时间窗: Day 0 to Day 7
virus-specific antibody levels in blood
次要结局
- Peak Tissue gene expression(Day 0 to Day 21)
- Peak nasal secretome(Day 0 to Day 21)
- Peak Nasal Virus quantity(Day 0 to day 21)
- Peak nasal neutrophils(Day 0 to Day 21)
- Peak Nasal virus anti-bodies(Day 0 to Day 21)
- Peak Day of blood virus anti-bodies(Day 0 to Day 21)
- Peak blood virus anti-bodies(Day 0 to Day 21)
- Peak Day of Tissue Gene Expression(Day 0 to Day 21)
- Peak Day of nasal secretome(Day 0 to Day 21)
- Peak Day of Nasal Virus quantity(Day 0 to day 21)
- Peak Day of nasal neutrophils(Day 0 to Day 21)
- Peak Day of Nasal virus anti-bodies(Day 0 to Day 21)
- Peak Symptom score(Day 0-21)
- Peak day of symptom score(Day 0-21)