Effects of Tobacco Products on Live Attenuated Influenza Virus (LAIV) Infections in Human Volunteers

NCT02019745 | Completed

• 2 other identifiers: 13-2246P50HL120100-01
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic exposure to (cigarette smoke) CS causes biological changes, including airway remodeling and changes in baseline gene expression profiles at the level of the epithelium. Our own data indicate that chronic exposure to CS suppresses the ability of epithelial cells to enhance antiviral gene expression in response to influenza infection and activate host defense responses. While there is a large body of evidence supporting the notion that exposure to CS causes significant changes in host defense responses, which may be linked to permanent changes in epithelial cells at the genomic level, it is not known whether new and emerging tobacco products have similar or distinct effects. Using live attenuated influenza virus (LAIV) inoculation in human volunteers, this study will compare influenza-induced responses in non-smokers (NS), cigarette smokers (CS), e-cigarette smokers (EC), hookah smokers (HS), and Little Cigar smokers (LCS) in vivo. This will be done by analyzing nasal viral titers, antiviral defense responses, inflammatory mediator production, and markers of immune responses for LAIV-induced responses between the different groups of volunteers.

Conditions

Influenza, Human; Smoking; Respiratory Tract Infections; Habits

Keywords

Live attenuated influenza virus (LAIV); Flu vaccine; FluMist; Smokers; New and emerging tobacco products

Outcome Measures

Primary Outcomes (1)

• Change in nasal responses of nonsmokers (NS), cigarette smokers (CS), e-cigarette smokers (EC), hookah smokers (HS), and Little Cigar smokers (LCS) to live attenuated influenza virus

  Influenza hemagglutinin (HA) messenger ribonucleic acid (mRNA) (normalized to β-actin) will be measured in nasal lavage fluid (NLF) cells from NS, CS, EC, HS, and LCS by quantitative real time-polymerase chain reaction (qRT-PCR) after LAIV inoculation.

  Baseline, 7 weeks

Secondary Outcomes (6)

• Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in numbers and activation of inflammatory and immune cells in NLF at specific time points compared to baseline

  Basline, 7 weeks

• Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for change in cytokines/chemokines and other mediators in NLF compared to baseline

  Baseline, 7 weeks

• Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in influenza-specific antibody production in NLF and serum

  Baseline, 7 weeks

• Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in mucus composition

  Basline, 7 weeks

• Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for genomic signatures induced in epithelial cells

  Baseline, 7 weeks

Study Arms (1)

LAIV (FluMist)

All subjects will receive a 0.2 mL dose of LAIV (FluMist) once during the study.

Biological: LAIV

Interventions

LAIV BIOLOGICAL

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

Also known as: FluMist

LAIV (FluMist)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

1. Nonsmokers 2. Cigarette smokers 3. Primarily e-cigarette smokers 4. Primarily hookah smokers 5. Primarily Little Cigar smokers

You may qualify if:

• Healthy, young nonsmoking adults age 18-45 years who are not routinely exposed to environmental tobacco smoke
• Healthy, young adults age 18-45 years who are active regular smokers (will be stratified based on cigarette, hookah, and Little Cigars)

You may not qualify if:

• Pregnancy or nursing;
• history of egg allergy;
• history of allergic rhinitis;
• aspirin therapy;
• asthma;
• immunodeficiency (HIV or other);
• on immunosuppressive drugs including corticosteroids;
• history of Guillain-Barre Syndrome;
• smokers with a forced expiratory volume in 1 second (FEV1) less than 75% predicted at screen;
• Chronic obstructive pulmonary disorder (COPD), cardiac disease, or any chronic cardiorespiratory condition;
• febrile and/or respiratory illness within past 3 weeks prior to entry into study

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Food and Drug Administration (FDA): collaborator
• Tobacco Centers of Regulatory Science (TCORS: collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Rebuli ME, Glista-Baker E, Hoffman JR, Duffney PF, Robinette C, Speen AM, Pawlak EA, Dhingra R, Noah TL, Jaspers I. Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial. Am J Respir Cell Mol Biol. 2021 Jan;64(1):126-137. doi: 10.1165/rcmb.2020-0164OC.

  PMID: 33095645 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, urine, nasal lavage fluid, nasal epithelial cells

MeSH Terms

Conditions

Influenza, Human; Smoking; Respiratory Tract Infections; Habits

Interventions

FluMist

Condition Hierarchy (Ancestors)

Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Behavior

Study Officials

• Ilona Jaspers, PhD

  University of North Carolina-Chapel Hill, Dept of Pediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 24, 2013
• Study Start: June 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: April 4, 2018

Record last verified: 2018-04

Locations

US (1)