Lung Innate Immunity and Microbiome After Tuberculosis Exposure

Last updated: January 17, 2025
Sponsor: University of Oxford
Overall Status: Active - Recruiting

Phase

N/A

Condition

Lung Disease

Hiv

Treatment

N/A

Clinical Study ID

NCT06526689
LIMBO-TB
  • Ages 18-65
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

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

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Adults aged 18-65 years

  2. Resident in or near London or Oxford for the duration of the study period

  3. Provide written informed consent

  4. Willing to allow the investigators to review the volunteer's review NHS care record,medical history, blood results and radiographs.

  5. Able and willing (in the investigator's opinion) to comply with all studyrequirements Group A and B Specific Inclusion Criteria

  6. Have undergone screening for TB through NHS services (including IGRA testing +/- CXRwhere indicated)

  7. Close contact with a sputum smear positive TB case within the last 12 weeks

Exclusion

Exclusion Criteria:

  1. Participation in another research study involving receipt of an investigationalproduct in the 30 days preceding enrolment or during the trial follow up period.

  2. History of anaphylaxis or any allergy likely to be exacerbated by any essentialstudy procedure

  3. History of currently poorly controlled of airways disease (including asthma),current cancer (except BCC of the skin or CIS of the cervix), bleeding disorder, ordrug or alcohol abuse

  4. Any significant autoimmune conditions or immunodeficiency (including HIV)

  5. Previous diagnosis or treatment for TB disease or latent TB infection

  6. Clinical, radiological, or laboratory evidence of current active TB disease

  7. Previous receipt of any investigational TB vaccines or aerosolised BCG.

  8. Clinically Significant abnormalities in spirometry.

  9. 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 arepermissible), or the use of other immunosuppressive agents concurrently or for morethan 14 days within the last 6 months

  10. Use of antibiotics in the past 4 weeks.

  11. Administration of immunoglobulins and/or any blood products within the three monthspreceding the planned study

  12. Administration of a live vaccine within the preceding 28 days prior to enrolment.

  13. Administration of any other non-live vaccine within the preceding 14 days prior toenrolment.

  14. Pregnancy or intention to become pregnant during study period

  15. Any other significant disease, disorder, or finding, which, in the opinion of theinvestigator, may either put the volunteer at risk, affect the volunteer's abilityto participate in the study or impair interpretation of the study data Group C Specific Exclusion Criteria

  16. History of close contact with case of TB, or previous contact tracing by TBservices.

Study Design

Total Participants: 50
Study Start date:
August 15, 2024
Estimated Completion Date:
October 01, 2028

Study Description

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:

  1. 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.

    The immune response to TB is also different in different people. Importantly, some people never develop a memory (or 'adaptive') immune response. This may suggest that the early immune response is able to clear all of the infection quickly in these people. Understanding differences in the early immune response would give us ways to develop more effective vaccines and treatments.

  2. Does the microbiome of the airway help in protecting people from TB? The bacteria of the microbiome live in unison with our cells, and are able to survive without causing an infection which makes us unwell. It has increasingly been understood that these bacteria help to "train" our immune system to work better. We will look at which bacteria are living normally in the airways of the people recruited to our study, and see how these bacteria change over time. This will help us to get a greater understanding of how the immune system and the microbiome work together, and if there is a role for the microbiome in preventing TB infections.

In summary this study will look at the early immune responses and the airway microbiome of people who have recently come into contact with the bacteria which causes TB. The differences that we identify could help us explain why some people have protection from TB, and provide us with novel approaches to developing new ways to protect others.

Connect with a study center

  • Churchill Hospital

    Oxford, Oxfordshire OX3 7LE
    United Kingdom

    Active - Recruiting

  • Centre for Clinical Vaccinology and Tropical Medicine

    Oxford, Oxon OX3 9DZ
    United Kingdom

    Active - Recruiting

  • Department of Respiratory Medicine, St Thomas' Hospital

    London, SE1 7EH
    United Kingdom

    Site Not Available

  • Grove Building, Royal Free NHS Foundation Trust

    London, NW3 2QG
    United Kingdom

    Active - Recruiting

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