NCT04901455

Responses to Live Attenuated Influenza Virus (LAIV) in Chronic Obstructive Pulmonary Disease (COPD)

Nasal Mucosal Immune Responses to Live Attenuated Influenza Virus (LAIV) in Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Phenotypes

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: University of North Carolina, Chapel Hill · Academic / Other
• Sex: All
• Age: 40 Years
• Healthy volunteers: Accepted

Summary

This study will determine the functional status of the nasal immune environment with LAIV exposure in COPD persons with frequent exacerbations (defined as individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months) and COPD persons without frequent exacerbations to determine acute exacerbation of COPD (AECOPD)-associated dysfunction in a) cytokines and immune effector cells of the nasal mucosa and b) viral replication. The investigators hypothesize that: 1) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate altered mucosal immune responses to LAIV exposure, and 2) COPD frequent exacerbators, compared to COPD infrequent exacerbators, will demonstrate increased markers of influenza viral replication after LAIV exposure.

Detailed description

This study is an early Phase 1, single-center, single-group unmasked exposure study of nasal immune responses after controlled exposure to LAIV. This trial will test the differences in the nasal immune responses to the nasal flu vaccine in two diseased groups of individuals along with healthy controls: COPD persons with frequent exacerbations (defined as individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months) and COPD persons without frequent exacerbations (defined as individuals with less than two episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months). A healthy control cohort will also be recruited, defined as individuals with spirometry-confirmed normal lung function and no asthma history. A total of 15 COPD frequent exacerbators, 15 infrequent exacerbators and 10 healthy controls will be enrolled for this trial. Investigators will balance the sex of participant as closely as possible to 50% male and 50% female. At screening visit, after obtaining informed consent and authorization to obtain medical records, all potential individuals will be screened for specific inclusion and exclusion criteria to ensure suitability and safety to receive the influenza nasal vaccine. A baseline assessment will be done including reviewing medical history and verifying eligibility, a physical exam by a study investigator, spirometry testing before and after bronchodilator, laboratory testing to screen for immunocompromised state \[Human Immunodeficiency Virus (HIV) antibody testing, compete blood count (CBC) with differential\], an assessment of symptoms, and pregnancy testing if pre-menopausal. Women who are pregnant, nursing, or women who are currently trying to become pregnant are not eligible for this study. Participants who meet eligibility after screening will be brought back for an enrollment visit where they will undergo a baseline assessment of their nasal inflammatory state. This includes sampling of the nose in three different ways. First, investigators will gently place a small strip of absorbent paper inside the lower part of the nose, and a nose clip will be applied for two minutes (ELF collection). Next, investigators will wash the inside of the nose with a small amount of sterile salt water to collect samples (NLF collection). Finally, investigators will take a small plastic device and gently scrape the inside of the nose to collect nasal cells (scraping collection). Investigators will also collect blood samples for inflammatory phenotyping. Within two weeks of enrollment visit, all enrolled individuals will receive the nasal influenza vaccine (there is no placebo component to the study). On days one, two, three, and seven after vaccine administration, participants will return to the study site to undergo nasal sampling including the nasal paper strip and washing, as well as blood collection. On Day 3, a nasal scraping will also be obtained. On Day 21 (optional visit), investigators will obtain nasal washing and blood collection. Investigators will collect patient reported outcomes using a validated influenza severity score to assess for unbiased correlations with biological measures.

Conditions

• COPD

Interventions

Type	Name	Description
BIOLOGICAL	LAIV	Standard dose of LAIV administered by a licensed health care providers.

Timeline

• Start date: 2022-10-03
• Primary completion: 2026-02-16
• Completion: 2026-02-16
• First posted: 2021-05-25
• Last updated: 2026-02-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study