HealthyEarly Phase 1NCT05027958
Characterization of Tissue-Specific Immune Responses to Bronchoscopic Instillation of Mycobacterial Antigens Into the Human Lung
A Early Phase 1 study testing Tuberculin Purified Protein Derivative in people with Healthy and Latent Tuberculosis Infection (LTBI), run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Healthy, Latent Tuberculosis Infection (LTBI)
- What is being tested?
- Tuberculin Purified Protein Derivative
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2022to 8 Dec 2024
- Phase
- Early Phase 1
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 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- If undergoing PET-CT imaging during this study places a participant over his/her annual radiation dose limit. Radiation exposure within the previous 12 months of >= 2.3 rem
- BMI > 40
- Diabetes
- Known life-threatening allergic reaction to Tuberculin, Lidocaine, Midazolam, Fentanyl or medications of similar classes
- Presence of any immunosuppressive diseases, including cancers with the exception of non-melanomatous skin cancer.
- Use of any systemic immunosuppressive medications, including corticosteroids (e.g., prednisone) or biological agents in the last 6 months prior to enrollment
- Any medical, psychiatric, social condition, occupational reason or other responsibility, in the judgement of the investigator, that is a contraindication to protocol participation or impairs a participant s ability to give informed consent
- Positive for COVID-19. (with-in 6 months prior to enrollment self-reported and or via PCR)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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....
Read the 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)
- Being tested
- Tuberculin Purified Protein Derivative
- Keywords
- Tuberculin Purified Protein Derivative, PPD, antigen-specific immune cells in airways
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tuberculin Purified Protein DerivativeDrug
PPD administered through the airways to elicit the development of alveolar inflammation challenge dose of 0.5 TU
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Tuberculin Purified Protein Derivative |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 5 and Day 21
Secondary outcomes (1)
Median Difference in the Standard Uptake Value (SUV)
Median difference in the Standard Uptake Value (SUV) in the pulmonary parenchyma and thoracic lymph nodes with positron emission tomography combined with chest computed tomography (PET-CT)
Measured: Baseline (Up to -7 days prior to PPD instillation), Day 4 and Day 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2021
- Study start3 May 2022
- Primary completion7 Nov 2024
- Study completion8 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kevin P Fennelly, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05027958
- Sponsor's protocol ID
- 210027
- Other IDs
- 21-H-0027
- Status last verified
- May 2026
- First submitted
- 28 Aug 2021
- Last updated
- 27 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant results data will be made available 6 months after publication date for a period of 5 year by sending a request to kevin.fennelly@nih.gov