Examining immune responses to a flu vaccine in COPD patients

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

This study is testing how well the flu vaccine works in people with COPD who have had different numbers of flare-ups, compared to healthy individuals.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Chapel Hill, North Carolina)
• Trial ID: NCT04901455 on ClinicalTrials.gov

What this trial studies

This study investigates how the nasal immune environment responds to a live attenuated influenza virus (LAIV) in individuals with chronic obstructive pulmonary disease (COPD), focusing on those with frequent and infrequent exacerbations. The trial will compare the immune responses and viral replication in COPD patients who have experienced two or more exacerbations in the past year to those who have had fewer. Additionally, a healthy control group will be included for comparison. The study aims to understand the differences in immune responses to the flu vaccine among these groups.

Who should consider this trial

Good fit: Ideal candidates include individuals aged over 40 with a physician diagnosis of COPD, specifically those with a history of frequent exacerbations.

Not a fit: Patients with acute exacerbations of COPD or those with significant nasal symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved vaccination strategies for COPD patients, potentially reducing the frequency of exacerbations.

How similar studies have performed: While there have been studies on influenza vaccination in COPD, this specific approach focusing on nasal immune responses is relatively novel.

Eligibility criteria

Inclusion Criteria:

In order to be eligible to participate in this study, an individual in the COPD group must meet all of the following criteria:

* Age\>40 years old
* Physician diagnosis of COPD confirmed by post-bronchodilator testing (defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)\< lower limit of normal and FEV1/FVC\<0.70) and FEV1\>30% predicted at screening
* Free of acute exacerbation of COPD for prior four weeks at time of recruitment
* Resting oxygen saturation \>94 percent
* Blood pressure systolic values between 90-160 mm Hg and diastolic between 55-90 mm Hg
* No nasal symptoms based on questionnaire
* Willingness and ability to participate in study procedures
* Completion of informed consent

In order to be eligible to participate in this study, an individual in the healthy control group must meet all of the following criteria:

* Age\>40 years old
* Spirometry testing showing normal lung function (defined as pre and post--bronchodilator FEV1/FVC\>=lower limit of normal and FEV1\>80 percent predicted) at screening
* Resting oxygen saturation \>94 percent
* Blood pressure systolic values between 90-160 mm Hg and diastolic between 55-90 mm Hg
* No nasal symptoms based on questionnaire
* Willingness and ability to participate in study procedures
* Completion of informed consent

Exclusion Criteria:

* Inability or unwillingness to consent
* Active tobacco or e-cigarette use (within last six months)
* Active diagnosis of asthma
* Any regular suppressive antibiotics (i.e., azithromycin)
* Daily oral prednisone use
* Any supplemental oxygen use beyond nocturnal oxygen therapy
* Use of intranasal corticosteroids in the 30 days prior to screening visit
* Chronic illness associated with immunosuppression (i.e., HIV, malignancy)
* History of documented or self-reported positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection requiring hospitalization
* Receipt of SARS-CoV-2 vaccine within 14 days prior to study screening visit or plan to receive SARS-CoV-2 vaccine from screening visit to 14 days after completion of all study procedures
* History of epistaxis, prior nasal surgery or anatomical abnormalities
* Current use of blood thinner beyond full dose aspirin \[e.g., warfarin (coumadin), clopidogrel (Plavix), dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis)\]
* Self-reported history of easy bruising or bleeding gums
* Serological evidence of HIV infection at screening (Positive HIV antibody test)
* Relative leukopenia (WBC\<4000), neutropenia (Absolute neutrophil count\<2000) or lymphopenia (absolute lymphocyte count\<1500) on screening CBC
* Respiratory infection (cough, sore throat, sinusitis, fever) within prior 4 weeks
* Active wheezing at day 0 visit
* Pregnancy or nursing or women who are currently trying to become pregnant. (All female subjects, except those who have had a hysterectomy with oophorectomy, will undergo urine pregnancy testing on the morning of the screening visit and again on the on Day 0 at the time of arrival to the lab and prior to LAIV administration. A positive pregnancy test will exclude the subject)
* Use of chronic immunosuppression in the 30 days prior to screening visit
* History of hypersensitivity, especially anaphylactic reactions, to egg proteins, gentamicin, gelatin, or arginine, or with a reaction to previous influenza vaccination at a severity level precluding the subject's participation as judged by the study physician
* History of Guillain-Barre syndrome
* Subjects who will be unable to avoid contact with immunocompromised individuals for 3 weeks after receiving LAIV vaccine
* Receipt of the LAIV during the current or prior flu vaccine season
* Physician diagnosed influenza, a positive test for influenza or suspicion of influenza illness in the 18 months prior to enrollment. Suspicion of influenza will be based on the CDC's influenza-like illness case definition ("fever\>100 °F AND cough/sore throat in the absence of a known cause other than influenza. Temperature can be measured in the office or at the home")
* Any condition that, in the opinion of the study investigator, would compromise the subject's ability to participate in the study

Where this trial is running

Chapel Hill, North Carolina

• Eastowne Medical Office Building — Chapel Hill, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Michael B Drummond, MD — University of North Carolina, Chapel Hill
• Study coordinator: Michael B Drummond, MD

Conditions COPD