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

NCT05027958 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 21002721-H-0027
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

Healthy; Latent Tuberculosis Infection (LTBI)

Keywords

Tuberculin Purified Protein Derivative; PPD; antigen-specific immune cells in airways

Outcome Measures

Primary Outcomes (1)

• Median Difference in CD4 Cell Response to Intrabronchial Instillation of Tuberculin Purified Protein Derivative (PPD)

  Median difference in CD4 cell response to intrabronchial instillation of Tuberculin Purified Protein Derivative (PPD) using flow cytometry. The frequency of (Mycobacterium tuberculosis) Mtb-specific T cells was measured by intracellular cytokine staining for Interferon Gamma (IFNγ) and Tumor Necrosis Factor (TNF) after in vitro restimulation of Peripheral Blood Mononuclear Cells (PBMC) and Bronchoalveolar Lavage (BAL) cells with PPD or Mtb-derived peptide megapools.

  Day 5 and Day 21

Secondary Outcomes (1)

• Median Difference in the Standard Uptake Value (SUV)

  Baseline (Up to -7 days prior to PPD instillation), Day 4 and Day 20

Study Arms (2)

Arm 1: Healthy Volunteer Participants with confirmed Latent Tuberculosis Infection (LTBI)

OTHER

Healthy volunteer participants with confirmed Latent Tuberculosis Infection (LTBI) (TST positive and IGRA positive) receiving instillation dose of purified protein derivative (PPD) 0.5 tuberculin units (10 uL Tubersol® in 10 mL normal saline) into the right upper lobe of lung.

Drug: Tuberculin Purified Protein Derivative

Arm 2: Healthy Volunteer Participants with confirmed non-Latent Tuberculosis Infection (LTBI)

OTHER

Healthy volunteer participants with confirmed non-Latent Tuberculosis Infection (LTBI) (TST negative and IGRA negative) receiving instillation dose of purified protein derivative (PPD) 0.5 tuberculin units (10 uL Tubersol® in 10 mL normal saline) into the right upper lobe of lung.

Drug: Tuberculin Purified Protein Derivative

Interventions

Tuberculin Purified Protein Derivative DRUG

PPD administered through the airways to elicit the development of alveolar inflammation challenge dose of 0.5 TU

Arm 1: Healthy Volunteer Participants with confirmed Latent Tuberculosis Infection (LTBI); Arm 2: Healthy Volunteer Participants with confirmed non-Latent Tuberculosis Infection (LTBI)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults 18-64 years old will be recruited for the two groups (non-LTBI controls vs confirmed LTBI). The lower limit of this age range is based on the need for invasive bronchoscopic procedures and exposure to radiation, both of which carry more risk at younger ages. In addition, most adults present with post-primary or reactivation TB that most often occurs radiographically in the upper lobes of the lungs, often with cavitation. Conversely, children and rare adults with primary TB have non-cavitary disease in the lower lobes. The higher limit of this age range is based on the known property of immune senescence, i.e., the waning of the strength of immune responses with advancing age.
• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 - 64 years of age
• No significant active medical problems. This would include but not limited to any cardiac disorder (e.g. arrhythmia, valvular disease), pulmonary disease (e.g. asthma requiring chronic medications, chronic bronchitis, emphysema, obstructive sleep apnea), kidney disease (e.g. nephritis, nephrosis), rheumatologic disorder (e.g. inflammatory arthritis), endocrine disorder (e.g. diabetes, thyroid disease), liver disease (e.g. hepatitis), gastrointestinal disorder (e.g. inflammatory bowel disease) or infectious disease (e.g. active tuberculosis).
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and agreement to use such a method during study participation

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnancy as assessed by urinary or plasma HCG or breastfeeding
• History of clinically significant respiratory dysfunction 3 months prior to participating
• Evidence of new pulmonary infection
• History of any chronic lung infections or chronic lung disease
• History of pulmonary hypertension
• Need for supplemental oxygen administration at rest
• Current use or inability to suspend use of anticoagulant therapy including platelet inhibitors (e.g. clopidogrel) within 7 days of study bronchoscopy or systemic anticoagulants (e.g. warfarin, enoxaparin, or DOAC) within 14 days of study bronchoscopy
• Any symptoms consistent with infection including fever, chills, night sweats, or unexplained weight loss
• A history of a necrotic reaction to a tuberculin skin test, including during screening
• A history of human immunodeficiency virus (HIV) infection
• A history of coughing up blood in the last 3 months
• Cigarette smoking, vaping or recreational drug use within the past 6 months (self-reported)
• If there is any discrepancy in tuberculin skin test and Interferon Gamma Release Assay test results (i.e. PPD+ but IGRA- or PPD- but IGRA+)
• Refusal or inability to undergo bronchoscopy, or a history of poor tolerance of a bronchoscopy

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

Tuberculin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Antigens, Bacterial; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antigens; Biological Factors

Results Point of Contact

• Title: Kevin P. Fennelly, M.D., MPH, ATSF
• Organization: Division of Intramural Research, NHLBI

kevin.fennelly@nih.gov

301-385-0807

Study Officials

• Kevin P Fennelly, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2021
• First Posted: August 31, 2021
• Study Start: May 3, 2022
• Primary Completion: November 7, 2024
• Study Completion: December 8, 2024
• Last Updated: November 6, 2025
• Results First Posted: November 6, 2025

Record last verified: 2025-01-16

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available 6 months after publication date for a period of 5 year
• Access Criteria: Sending request to kevin.fennelly@nih.gov

Locations

US (1)