NCT05027958

Characterization of Tissue-Specific Immune Responses to Bronchoscopic Instillation of Mycobacterial Antigens Into the Human Lung

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) · NIH
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

Background: Tuberculosis (TB) is a lung disease. It is caused by inhaling a type of airborne bacterium. Tuberculin Purified Protein Derivative (PPD) is used to test for TB exposure. It is usually injected under a person s skin. In this study, it will be applied in the lung. Objective: To learn how the cells within the lung react (immune response) when exposed to PPD. Eligibility: Adults ages 18-64 who (1) have been exposed to TB but do not have active disease or symptoms or (2) have never been exposed to TB. Design: Participants will be screened with a medical history, physical exam, and blood tests. They will have a TB skin test. They will also have an electrocardiogram to examine heart rhythm. For this, sticky patches will be placed on their chest. Some screening tests will be repeated at study visits. Participants will have 3 FDG PET-CT scans. They will lie in a machine that creates pictures of the inside of their body. They will get a radioactive substance injected into their arm called 18FDG. It helps make the pictures. Participants will have 3 bronchoscopies. Their mouth and nasal airways will be numbed. They will get drugs to relax. A tube will be inserted through their nose or mouth into a lung. Fluid will be delivered into the lung and suctioned back out to collect cells. They will get PPD during the first bronchoscopy. Participation will last for about 30 days. Participants will visit the clinic up to 8 times. They will go home after each procedure. No hospital stays are needed....

Detailed description

Study Description: We propose a pilot study in which we employ directed bronchoscopic instillation of Mycobacterium tuberculosis (Mtb)-Tuberculin Purified Protein Derivative (PPD) to evaluate local airway immune response in adults with or without latent tuberculosis infection (LTBI). Primary Objective: The primary objective of this study is to understand the pulmonary immune response to mycobacterial antigens by determining the persistence of antigen-specific immune cells in the airways versus circulation after local bronchoscopic instillation of Tuberculin Purified Protein Derivative (PPD) into the lungs of adults with or without LTBI. Secondary Objective: The secondary objective is to characterize the location and persistence of immune cell activity in the pulmonary parenchyma and thoracic lymph nodes with positron emission tomography combined with chest computed tomography (PET-CT) after bronchoscopic Tuberculin Purified Protein Derivative (PPD) instillation in adults with or without LTBI. Exploratory Objectives: (a) An exploratory objective will be to perform phenotypic and functional analysis of immune cell populations in the airways vs circulation following bronchoscopic instillation of Tuberculin Purified Protein Derivative (PPD) into the lungs of individuals with or without LTBI. (b) An additional exploratory objective will be to characterize the production of soluble mediators (including but not limited to: cytokines, lipid mediators, and defensins) in BAL fluid vs blood within the same context. Endpoints: Primary Endpoint: The primary endpoint will be the enumeration of Mtb antigen-specific CD4+ and CD8+ T cell populations in the airway and peripheral blood at early and late time points after bronchoscopic Tuberculin Purified Protein Derivative (PPD) instillation. Secondary Endpoint: The secondary endpoint will be the quantification of \[18F\]fluoro-D-glucose (FDG) uptake in adjacent pulmonary parenchyma and draining thoracic lymph nodes via PET-CT at early and late time points after PPD instillation. Exploratory Endpoints: (a) An exploratory endpoint will be the quantification of frequencies of cell surface molecules, intracellular cytokines and transcription factors among immune cell populations in the airways vs circulation following bronchoscopic instillation of Tuberculin Purified Protein Derivative (PPD) into the lungs of individuals with or without LTBI. (b) An exploratory endpoint will involve the identification and quantification of soluble mediators in the airway and peripheral blood after PPD instillation in the lungs within the same context.

Conditions

• Healthy
• Latent Tuberculosis Infection (LTBI)

Interventions

Type	Name	Description
DRUG	Tuberculin Purified Protein Derivative	PPD administered through the airways to elicit the development of alveolar inflammation challenge dose of 0.5 TU

Timeline

• Start date: 2022-05-03
• Primary completion: 2024-11-07
• Completion: 2024-12-08
• First posted: 2021-08-31
• Last updated: 2025-11-06
• Results posted: 2025-11-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study