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

• Status: Not yet recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

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....

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

• 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 any anticoagulant therapy including platelet inhibitors (e.g. aspirin, NSAIDs, within 7 days, clopidogrel or systemic anticoagulants (warfarin, lovenox, or DOAC)within 14 days of study bronchoscopy or inability to suspend aspirin 7 days prior to 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 (selfreported)

• 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

• 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)