Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05027958
Other study ID # 210027
Secondary ID 21-H-0027
Status Recruiting
Phase Early Phase 1
First received
Last updated
Start date May 3, 2022
Est. completion date January 1, 2026

Study information

Verified date March 6, 2024
Source National Institutes of Health Clinical Center (CC)
Contact Sandra Cooper Bennett, R.N.
Phone (240) 328-0465
Email sandra.cooper@nih.gov
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 100
Est. completion date January 1, 2026
Est. primary completion date January 1, 2026
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 64 Years
Eligibility - INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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 - 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)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Tuberculin Purified Protein Derivative
PPD administered through the airways to elicit the development of alveolar inflammation challenge dose of 0.5 TU

Locations

Country Name City State
United States National Institutes of Health Clinical Center Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary pulmonary immune response to mycobacterial antigens To understand the pulmonary immune response to mycobacterial antigens by determining the longevity 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. 30 days
Secondary location and longevity of immune cell activity in the pulmonary parenchyma and thoracic lymph nodes characterize the location and longevity 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. 30 days
See also
  Status Clinical Trial Phase
Recruiting NCT06052553 - A Study of TopSpin360 Training Device N/A
Completed NCT05511077 - Biomarkers of Oat Product Intake: The BiOAT Marker Study N/A
Recruiting NCT04632485 - Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
Completed NCT05931237 - Cranberry Flavan-3-ols Consumption and Gut Microbiota in Healthy Adults N/A
Completed NCT04527718 - Study of the Safety, Tolerability and Pharmacokinetics of 611 in Adult Healthy Volunteers Phase 1
Terminated NCT04556032 - Effects of Ergothioneine on Cognition, Mood, and Sleep in Healthy Adult Men and Women N/A
Completed NCT04998695 - Health Effects of Consuming Olive Pomace Oil N/A
Completed NCT04107441 - AX-8 Drug Safety, Tolerability and Plasma Levels in Healthy Subjects Phase 1
Completed NCT04065295 - A Study to Test How Well Healthy Men Tolerate Different Doses of BI 1356225 Phase 1
Completed NCT01442831 - Evaluate the Absorption, Metabolism, And Excretion Of Orally Administered [14C] TR 701 In Healthy Adult Male Subjects Phase 1
Terminated NCT05934942 - A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood Phase 1
Recruiting NCT05525845 - Studying the Hedonic and Homeostatic Regulation of Food Intake Using Functional MRI N/A
Completed NCT05515328 - A Study in Healthy Men to Test How BI 685509 is Processed in the Body Phase 1
Completed NCT04967157 - Cognitive Effects of Citicoline on Attention in Healthy Men and Women N/A
Completed NCT05030857 - Drug-drug Interaction and Food-effect Study With GLPG4716 and Midazolam in Healthy Subjects Phase 1
Recruiting NCT04714294 - Evaluate the Safety, Tolerability and Pharmacokinetics Characteristics of HPP737 in Healthy Volunteers Phase 1
Recruiting NCT04494269 - A Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls Phase 1
Completed NCT04539756 - Writing Activities and Emotions N/A
Recruiting NCT04098510 - Concentration of MitoQ in Human Skeletal Muscle N/A
Completed NCT03308110 - Bioavailability and Food Effect Study of Two Formulations of PF-06650833 Phase 1