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

NCT04901455 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: 21-02541R01HL150081-01A1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Difference in mucosal immune response between COPD frequent exacerbators and COPD infrequent exacerbators

  Epithelial lining fluid interferon-gamma (INF-ɣ) area under the curve (AUC) from day 0 (baseline) to day 3 (pg/mL x days)

  Baseline, Day 3

Secondary Outcomes (1)

• Difference in viral clearance between COPD frequent exacerbators and COPD infrequent exacerbators

  Baseline, Day 3

Study Arms (3)

COPD Frequent Exacerbators

EXPERIMENTAL

Individuals with two or more episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months

Biological: LAIV

COPD Infrequent Exacerbators

EXPERIMENTAL

Individuals with less than two episodes of worsening in COPD symptoms requiring treatment with antibiotics and/or steroids in the prior 12 months

Biological: LAIV

Healthy Control

EXPERIMENTAL

Individuals with spirometry-confirmed normal lung function and no asthma history

Biological: LAIV

Interventions

LAIV BIOLOGICAL

Standard dose of LAIV administered by a licensed health care providers.

Also known as: FluMist

COPD Frequent Exacerbators; COPD Infrequent Exacerbators; Healthy Control

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 based on spirometry testing available in the prior year or completed at screening (if no historical testing available)
• 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) based on spirometry testing available in the prior year or completed at screening (if no historical testing available)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Eastowne Medical Office Building

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

FluMist

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael B Drummond, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open label exposure study.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is an early Phase 1, single-center, parallel-group unmasked exposure study of nasal immune responses after controlled exposure to LAIV.

Study Record Dates

• First Submitted: May 20, 2021
• First Posted: May 25, 2021
• Study Start: October 3, 2022
• Primary Completion: February 16, 2026
• Study Completion: February 16, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months following publication through 36 months after publication
• Access Criteria: Proposing investigator has IRB, IEC, or REB approval and an executed data use/sharing agreement with UNC.

Locations

US (1)