TuberculosisLIMBO-TBNCT06526689
Lung Innate Immunity and Microbiome After Tuberculosis Exposure
An observational study of Tuberculosis and Latent Tuberculosis, run by University of Oxford at 3 sites in United Kingdom.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Latent Tuberculosis
- How many people
- 50 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 15 Aug 2024to 1 Oct 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Human Adults with and with our recent exposure to M.tb
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom3 sites, 3 recruiting
- Recruiting
Grove Building, Royal Free NHS Foundation Trust
London, NW3 2QG
Marc Lipman, M.D
David Lowe, PhD
- Recruiting
Churchill Hospital
Oxford, Oxfordshire, OX3 7LE
Timothy Fresdgaard-Jones, MRCP
- Recruiting
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxon, OX3 9DZ
Timothy PW Fredsgaard-Jones, MBBS, timothy.fredsgaard-jones@ndm.ox.ac.uk
About this study
Official title: Investigating the Impact of the Pulmonary Innate Immune Response and Microbiome After Exposure to Mycobacterium Tuberculosis
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
Read the detailed 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:
- 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.
- 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.
- Conditions
- Tuberculosis, Latent Tuberculosis
- Medical subject headings
- Tuberculosis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Adult volunteers who are recent contacts of Mycobacterium tuberculosis sputum smear positive cases with positive IGRA | |
| Group B | Adult volunteers who are recent contacts of Mycobacterium tuberculosis sputum smear positive cases with negative IGRA | |
| Group C | Healthy adult volunteers with no previous exposure to Mycobacterium tuberculosis. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The immunological response after recent M.tb exposure measured as the differentials of innate immune cells in the blood and sputum.
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.
Measured: At enrolment and Day 84
Secondary outcomes (1)
An assessment of respiratory microbiome diversity in M.tb contacts compared to healthy controls
To characterise the respiratory microbiome after exposure to M.tb by identifying bacterial genetic sequences and calculating both alpha diversity and beta diversity of sputum samples. Baseline and followup sample at day 84 will be investigated to determine robustness of communities.
Measured: At enrolment and Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2024
- Study start15 Aug 2024
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London
- Responsible party
- Sponsor
- Investigators
- Helen McShane, PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06526689
- Sponsor's protocol ID
- LIMBO-TB
- Acronym
- LIMBO-TB
- Status last verified
- Jan 2025
- First submitted
- 15 May 2024
- Last updated
- 22 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Impact of the Pulmonary Innate Immune Response and Microbiome After Exposure to Mycobacterium Tuberculosis
- ClinicalTrials.gov ID
- NCT06526689
- Acronym / sponsor ID
- LIMBO-TB / LIMBO-TB
- Conditions
- Tuberculosis, Latent Tuberculosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- University College, London
- Study start
- 15 Aug 2024 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 30 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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:
- 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.
- 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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | – | –Adult volunteers who are recent contacts of Mycobacterium tuberculosis sputum smear positive cases with positive IGRA |
| Group B | – | –Adult volunteers who are recent contacts of Mycobacterium tuberculosis sputum smear positive cases with negative IGRA |
| Group C | – | –Healthy adult volunteers with no previous exposure to Mycobacterium tuberculosis. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Human Adults with and with our recent exposure to M.tb
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The immunological response after recent M.tb exposure measured as the differentials of innate immune cells in the blood and sputum.
Time frame: 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.
1 secondary outcome
An assessment of respiratory microbiome diversity in M.tb contacts compared to healthy controls
Time frame: At enrolment and Day 84
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Helen McShane, PhD principal investigator
University of Oxford
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Latent Tuberculosis, run by University of Oxford at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Timothy Fredsgaard-Jones, MBBS (+44 (0)1865 611385, timothy.fredsgaard-jones@ndm.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The immunological response after recent M.tb exposure measured as the differentials of innate immune cells in the blood and sputum. (time frame: At enrolment and Day 84). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2025.