Investigating Immune Responses to Aerosol BCG Challenge in Healthy UK Adults
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- 65
Summary
- Conditions
- Tuberculosis
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: Triple (Participant, Care Provider, Outcomes Assessor)Masking Description: Volunteers in groups 1-5 will be blinded to eliminate subject bias (either conscious or subconscious) using a 10:3 randomised control design (BCG:placebo) whereby volunteers randomised to the BCG arms (Arm A) will inhale aerosolised BCG mixed with normal saline and those randomised to the placebo arms (Arm B) will inhale aerosolised normal saline. The volunteers will be unblinded just prior to the 3 month visit when those in Arm A may have sputum collected and those in Arm B will not. Volunteers in group 6 and 7 will not be blinded. For groups 1 -5, the bronchoscopist performing the procedure will also be blinded to eliminate any bias in the reporting of the appearance of the lung mucosa and extent of airway inflammation. All samples will be anonymised and the subject number will be allocated sequentially and therefore not identifiable with the allocated Arm. The senior immunologist will be blinded to reduce any bias that could be introduced at the sample processing stage.Primary Purpose: Other
Participation Requirements
- Age
- Between 18 years and 50 years
- Gender
- Both males and females
Description
Mycobacterium tuberculosis (M.tb) is a pathogen with worldwide preponderance that infects humans and causes the transmissible disease tuberculosis (TB). An estimated one-third of the world's population is latently infected with M.tb, carrying a 10% lifetime risk of developing active life-threatening...
Mycobacterium tuberculosis (M.tb) is a pathogen with worldwide preponderance that infects humans and causes the transmissible disease tuberculosis (TB). An estimated one-third of the world's population is latently infected with M.tb, carrying a 10% lifetime risk of developing active life-threatening disease. In 2016, there were 10 million new cases worldwide and 1.7 million people died of TB. Co-infection with human immunodeficiency virus (HIV) greatly increases the risk of TB reactivation and death. Diagnosis is challenging and drug treatment is often harmful, costly and complex. For these reasons, it is essential to develop a more effective vaccine against TB. An improved understanding of the nature of protective immunity in humans would significantly improve rational vaccine development. Whilst host immunity, particularly systemic adaptive immunity, has been well characterized in murine models, the understanding of the immunological events that occur in humans during acute infection is limited. In particular, the knowledge of human mucosal responses to M.tb. is limited. This is primarily due to the difficulties in studying early disease processes in the lung. Consequently, the majority of human studies have investigated immune responses ex-vivo in peripheral blood or after in-vitro infection of cell lines. A better understanding of the immune components that exist at the respiratory mucosal surfaces in humans could lead to interventions that prevent infection at the point of entry. TB043 is a clinical challenge trial primarily to evaluate the safety of BCG challenge administered by the aerosol inhaled route in healthy, BCG naive UK adults. The trial will also look to evaluate and compare the amount of BCG recovered from the lungs as various points after challenge, allowing investigation into the immune components at mucosal surfaces.
Tracking Information
- NCT #
- NCT03912207
- Collaborators
- Wellcome Trust
- National Institute for Health Research, United Kingdom
- Investigators
- Principal Investigator: Professor Helen McShane University of Oxford
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