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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Show all 23Show fewer

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

Other trials in United States

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.

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 groups in NCT05027958
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.

3 May 20228 Dec 2024

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)

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Characterization of Tissue-Specific Immune Responses to Bronchoscopic Instillation of Mycobacterial Antigens Into the Human Lung
ClinicalTrials.gov ID: NCT05027958
Acronym / sponsor ID: 210027
Conditions: Healthy, Latent Tuberculosis Infection (LTBI)
Keywords: Tuberculin Purified Protein Derivative, PPD, antigen-specific immune cells in airways
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
Study start: 3 May 2022 (actual)
Primary completion: 7 Nov 2024 (actual)
Study completion: 8 Dec 2024 (actual)
First posted: 31 Aug 2021 (actual)
Results: Posted 6 Nov 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

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:

Some screening tests will be repeated at study visits.

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

Endpoints:

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Single blind (investigator)
Number of arms: 2

Arm	Type	Receives
Arm 1: Healthy Volunteer Participants with confirmed Latent Tuberculosis Infection (LTBI)	Other	Drug: Tuberculin Purified Protein DerivativeHealthy 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.
Arm 2: Healthy Volunteer Participants with confirmed non-Latent Tuberculosis Infection (LTBI)	Other	Drug: Tuberculin Purified Protein DerivativeHealthy 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.

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

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

Key exclusion criteria (23 listed)

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
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Tuberculin Purified Protein DerivativePPD administered through the airways to elicit the development of alveolar inflammation challenge dose of 0.5 TU	Drug	Arm 1: Healthy Volunteer Participants with confirmed Latent Tuberculosis Infection (LTBI), Arm 2: Healthy Volunteer Participants with confirmed non-Latent Tuberculosis Infection (LTBI)

Primary outcome

Median Difference in CD4 Cell Response to Intrabronchial Instillation of Tuberculin Purified Protein Derivative (PPD)
Time frame: Day 5 and Day 21
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.

1 secondary outcome

Median Difference in the Standard Uptake Value (SUV)
Time frame: Baseline (Up to -7 days prior to PPD instillation), Day 4 and Day 20

Results and safety

Results posted to the registry on 6 Nov 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1: Healthy Volunteer Participants With Confirmed Latent Tuberculosis Infection (LTBI)	7	4
Arm 2: Healthy Volunteer Participants With Confirmed Non-Latent Tuberculosis Infection (LTBI)	10	4

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

Time frame: Day 5 and Day 21. Median (Inter-Quartile Range). Unit: % Antigen Specific T cells

Measure	Arm 1: Healthy Volunteer Participants With Confirmed Latent Tuberculosis Infection (LTBI) n = 4	Arm 2: Healthy Volunteer Participants With Confirmed Non-Latent Tuberculosis Infection (LTBI) n = 4
Day 5	5.26 (3.99 to 11.5)	0.725 (0.462 to 1.74)
Day 21	29.9 (19 to 37.3)	2.92 (1.98 to 4.16)

Arm 1: Healthy Volunteer Participants With Confirmed Latent Tuberculosis Infection (LTBI) vs Arm 2: Healthy Volunteer Participants With Confirmed Non-Latent Tuberculosis Infection (LTBI): p = 0.05714, Wilcoxon (Mann-Whitney)

Population analysed: Cryo-recovery of cells obtained from one participant was unsuccessful; therefore, analysis could not be performed.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 30 Days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1: Healthy Volunteer Participants With Confirmed Latent Tuberculosis Infection (LTBI)	0 of 7 (0%)	5 of 7 (71.4%)	0 of 7
Arm 2: Healthy Volunteer Participants With Confirmed Non-Latent Tuberculosis Infection (LTBI)	0 of 10 (0%)	6 of 10 (60%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Individual participant dataSharing planned: 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

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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. This study is not recruiting at the moment.

Kevin P Fennelly, M.D. principal investigator

National Heart, Lung, and Blood Institute (NHLBI)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 23 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: finished, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Difference in CD4 Cell Response to Intrabronchial Instillation of Tuberculin Purified Protein Derivative (PPD) (time frame: Day 5 and Day 21). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05027958.

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 27 May 2026.