Investigating the Impact of the Pulmonary Innate Immune Response and Microbiome After Exposure to Mycobacterium Tuberculosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- The immunological response after recent M.tb exposure measured as the differentials of innate immune cells in the blood and sputum.
研究概览
简要总结
To characterise the innate pulmonary immune response and respiratory microbiome after recent exposure to M.tb and to evaluate how differences determine the outcome of M.tb exposure
详细描述
Tuberculosis (TB) kills more people than any other single infectious disease. It is estimated that 1 in 4 people are infected with the bug that causes TB. We really need an effective vaccine to prevent people getting TB, but we don't understand what sort of immune response is needed to protect people.
The very early response to infection, called the innate immune response, is not well understood in TB, partly because it is difficult to study, as most of the changes happen before people get symptoms. In a recent study we have seen that human infection with BCG, a bacteria similar to the one that causes TB, results in significant changes in the early immune response in the lungs, which are not seen in the blood.
The immune system is constantly coming into contact with different bacteria which live on the surfaces of our bodies, called the microbiome, this includes the linings of the airways (the tubes of the lungs). Understanding the interactions between the microbiome in the airways and immune system can help us to understand why some people can resist developing TB.
This study has been designed to help to answer two key questions about the early immune responses to TB:
- What is the early immune response to TB, and how does it vary between people? We will use samples of sputum from people who have recently been living with someone with an active TB infection. We will measure the type of immune cells present in these samples and how they change over time, comparing what we find with blood results. This will help us to build a picture of what is happening both in the airways and in the blood during the early immune responses to TB.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
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
- •Adults aged 18-65 years
- •Resident in or near London or Oxford for the duration of the study period
- •Provide written informed consent
- •Willing to allow the investigators to review the volunteer's review NHS care record, medical history, blood results and radiographs.
- •Able and willing (in the investigator's opinion) to comply with all study requirements
- •Group A and B Specific Inclusion Criteria
- •Have undergone screening for TB through NHS services (including IGRA testing +/- CXR where indicated)
- •Close contact with a sputum smear positive TB case within the last 12 weeks
排除标准
- •Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment or during the trial follow up period.
- •History of anaphylaxis or any allergy likely to be exacerbated by any essential study procedure
- •History of currently poorly controlled of airways disease (including asthma), current cancer (except BCC of the skin or CIS of the cervix), bleeding disorder, or drug or alcohol abuse
- •Any significant autoimmune conditions or immunodeficiency (including HIV)
- •Previous diagnosis or treatment for TB disease or latent TB infection
- •Clinical, radiological, or laboratory evidence of current active TB disease
- •Previous receipt of any investigational TB vaccines or aerosolised BCG.
- •Clinically Significant abnormalities in spirometry.
- •Concurrent use of oral, inhaled or systemic steroid medication or use for more than 14 days within the last 6 months (steroids used as a cream or ointment are permissible), or the use of other immunosuppressive agents concurrently or for more than 14 days within the last 6 months
- •Use of antibiotics in the past 4 weeks.
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned study
- •Administration of a live vaccine within the preceding 28 days prior to enrolment.
- •Administration of any other non-live vaccine within the preceding 14 days prior to enrolment.
- •Pregnancy or intention to become pregnant during study period
- •Any other significant disease, disorder, or finding, which, in the opinion of the investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the study or impair interpretation of the study data
- •Group C Specific Exclusion Criteria
- •History of close contact with case of TB, or previous contact tracing by TB services.
结局指标
主要结局
The immunological response after recent M.tb exposure measured as the differentials of innate immune cells in the blood and sputum.
时间窗: At enrolment and Day 84
We will characterise the number and activity of early immunological response to M.tb in the respiratory tract and systemic circulation. Samples of blood and sputum will be utilised to enumerate the proportions of innate immune cells measured by flow cytometry and their activity.
次要结局
- An assessment of respiratory microbiome diversity in M.tb contacts compared to healthy controls(At enrolment and Day 84)