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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborators:
Food and Drug Administration (FDA)
Tobacco Centers of Regulatory Science (TCORS
Information provided by (Responsible Party):
Ilona Jaspers, PhD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02019745
First received: December 18, 2013
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Influenza, Human
Smoking
Respiratory Tract Infections
Habits
Biological: LAIV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effects of Tobacco Products on Live Attenuated Influenza Virus (LAIV) Infections in Human Volunteers

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline, 7 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: Basline, 7 weeks ] [ Designated as safety issue: No ]
  • Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for change in cytokines/chemokines and other mediators in NLF compared to baseline [ Time Frame: Baseline, 7 weeks ] [ Designated as safety issue: No ]
    Cytokines and chemokines and other mediators to be measured include, but are not limited to, interferon gamma-induced protein (IP)-10, interleukin (IL)-6, IL-1beta, interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumor necrosis factor (TNF)alpha, IL-8, RANTES, eotaxins, prostaglandin E2 (PGE2), eosinophil cationic protein (ECP), and myeloperoxidase (MPO).

  • Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in influenza-specific antibody production in NLF and serum [ Time Frame: Baseline, 7 weeks ] [ Designated as safety issue: No ]
    Immunoglobulin (Ig)A will be analyzed in NLF while IgG and IgM will be analyzed in the serum.

  • Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in mucus composition [ Time Frame: Basline, 7 weeks ] [ Designated as safety issue: No ]
  • Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for genomic signatures induced in epithelial cells [ Time Frame: Baseline, 7 weeks ] [ Designated as safety issue: No ]
  • Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for epigenomic signatures induced in epithelial cells [ Time Frame: Baseline, 7 weeks ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

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


Estimated Enrollment: 100
Study Start Date: June 2014
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
LAIV (FluMist)
All subjects will receive a 0.2 mL dose of LAIV (FluMist) once during the study.
Biological: LAIV
Standard dose of LAIV administered by a licensed health care providers.
Other Name: FluMist

Detailed Description:

Cigarette smoke (CS), e-cigarette smoke (EC), hookah smoke (HS), and Little Cigar smoke (LCS)-exposed populations will be stratified based on their responses to a smoking diary, protocol questionnaire, as well as urine cotinine levels (which should be present in all three groups). We are aware that many current smokers are poly-tobacco product users (i.e. smoke cigarettes in addition to non-cigarette products), which could be confounding our observations. This will be controlled for by having potential volunteers complete a smoking diary and provide daily urine samples for 1 week prior to enrolling in the study. Based on this diary, subjects will be grouped as CS (cigarettes only), EC (e-cigarette smokers and smoking less than ½ pack of cigarettes per week), HS (hookah smokers and smoking less than ½ pack of cigarettes per week), and LCS (little cigar smokers and smoking less than ½ pack of cigarettes per week). Individuals with mixed exposures that exceed those described above (i.e. smoking more than ½ pack of cigarettes per week in addition to smoking hookah, e-cigarettes, or Little Cigars) will be excluded from the studies. Potential subjects will then complete a questionnaire regarding their smoking history, and will undergo urine collection for measurement of cotinine for 7 consecutive days. Subjects will be assigned to the different groups as followed: Group NS (no routine exposure to tobacco smoke, and average log10 urine cotinine/creatinine ratio < 1.0), Group CS (active cigarette smoker and log10 urine cotinine/creatinine ratio > 4), Group EC (active e-cigarette smokers and average log10 urine cotinine/creatinine ratio 1-4), Group HS (active routine hookah smokers and average log10 urine cotinine/creatinine ratio 1-4), or Group LCS (active routine Little Cigars smoker and average log10 urine cotinine/creatinine ratio 1-4).

Study protocol outline:

Screening visit (2-4 weeks prior to Day 0): Obtain informed consent, history (including smoke exposure questionnaire), physical examination, vital signs (VS), blood draw (for anti-influenza antibody titer, HIV and T cell stimulation with flu antigen), urine (for cotinine), nasal lavage (NL, for differential cell count, viral culture and antigen detection, cytokine panel), nasal epithelial biopsy (NB) #1, pregnancy test for females of child bearing potential. In addition, smokers will undergo spirometry.

Subjects will return to the research lab daily the for the week prior to D0 to provide a urine sample for cotinine. Subjects will given a daily smoking/exposure diary during this time to continue throughout the study.

Day 0 (Monday): Obtain VS, NL, urine. Administer FluMist.

Day 1 (Tuesday): Obtain VS, NL, urine, NB #2

Day 2 (Wednesday): Obtain VS, NL, urine

Day 8 +/- 1 day (Monday-Wednesday): Obtain VS, NL, urine, NB #3

Day 21 +/- 7 days: Obtain VS, blood draw, collect completed smoking/exposure diary

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02019745

Contacts
Contact: Martha Almond, RRT 919-966-0759 martha_almond@med.unc.edu
Contact: Carole Robinette, CPFT, MS 919-966-5638 carole_robinette@med.unc.edu

Locations
United States, North Carolina
Center for Environmental Medicine, Asthma and Lung Biology Recruiting
Chapel Hill, North Carolina, United States, 27599
Principal Investigator: Ilona Jaspers, PhD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Food and Drug Administration (FDA)
Tobacco Centers of Regulatory Science (TCORS
Investigators
Principal Investigator: Ilona Jaspers, PhD University of North Carolina-Chapel Hill, Dept of Pediatrics
  More Information

No publications provided

Responsible Party: Ilona Jaspers, PhD, Associate Professor, Department of Pediatrics, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02019745     History of Changes
Other Study ID Numbers: 13-2246, P50HL120100-01
Study First Received: December 18, 2013
Last Updated: June 17, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government
United States: Food and Drug Administration

Keywords provided by University of North Carolina, Chapel Hill:
Live attenuated influenza virus (LAIV)
Flu vaccine
FluMist
Smokers
New and emerging tobacco products

Additional relevant MeSH terms:
Smoking
Virus Diseases
Respiratory Tract Diseases
Influenza, Human
Respiratory Tract Infections
Orthomyxoviridae Infections
RNA Virus Infections
Infection
Habits
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014