Influenza, HumanNCT02019745
Effects of Tobacco Products on Live Attenuated Influenza Virus (LAIV) Infections in Human Volunteers
An observational study of Influenza, Human and Smoking, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human, Smoking, Respiratory Tract Infections
- What is being tested?
- LAIV
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Jun 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: 1. Nonsmokers 2. Cigarette smokers 3. Primarily e-cigarette smokers 4. Primarily hookah smokers 5. Primarily Little Cigar smokers
Who may be able to join
- 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)
Who cannot join
- Pregnancy or nursing;
- history of egg allergy;
- history of allergic rhinitis;
- aspirin therapy;
- asthma;
- immunodeficiency (HIV or other);
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Environmental Medicine, Asthma and Lung Biology
Chapel Hill, North Carolina, 27599
About this study
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.
Read the 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 lining fluid (ELF, collected with filter paper for cytokine analysis), 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, ELF, urine. Administer FluMist.
Day 1 (Tuesday): Obtain VS, NL, ELF, urine, NB #2
Day 2 (Wednesday): Obtain VS, NL, ELF, urine
Day 8 +/- 1 day (Monday-Wednesday): Obtain VS, NL, ELF, urine, NB #3
Day 21 +/- 7 days: Obtain VS, blood draw, collect completed smoking/exposure diary
- Conditions
- Influenza, Human, Smoking, Respiratory Tract Infections, Habits
- Being tested
- LAIV
- Keywords
- Live attenuated influenza virus (LAIV), Flu vaccine, FluMist, Smokers, New and emerging tobacco products
- Medical subject headings
- Influenza, Human, Smoking, Respiratory Tract Infections, Habits
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LAIVBiological
Also called FluMist
Standard dose of LAIV administered by a licensed health care providers.
| Study group | Role | What they receive |
|---|---|---|
| LAIV (FluMist) | All subjects will receive a 0.2 mL dose of LAIV (FluMist) once during the study. Receives: Biological: LAIV |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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
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).
Measured: 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
Immunoglobulin (Ig)A will be analyzed in NLF while IgG and IgM will be analyzed in the serum.
Measured: Baseline, 7 weeks
Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in mucus composition
Measured: Basline, 7 weeks
Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for genomic signatures induced in epithelial cells
Measured: Baseline, 7 weeks
Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for epigenomic signatures induced in epithelial cells
Measured: Baseline, 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study startJun 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Influenza, HumanStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Food and Drug Administration (FDA), Tobacco Centers of Regulatory Science (TCORS
- Responsible party
- Sponsor
- Investigators
- Ilona Jaspers, PhD, Principal investigator, University of North Carolina-Chapel Hill, Dept of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02019745
- Sponsor's protocol ID
- 13-2246
- Other IDs
- P50HL120100-01
- Status last verified
- Apr 2018
- First submitted
- 18 Dec 2013
- Last updated
- 4 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 33095645
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Tobacco Products on Live Attenuated Influenza Virus (LAIV) Infections in Human Volunteers
- ClinicalTrials.gov ID
- NCT02019745
- Acronym / sponsor ID
- 13-2246
- Conditions
- Influenza, Human, Smoking, Respiratory Tract Infections, Habits
- Keywords
- Live attenuated influenza virus (LAIV), Flu vaccine, FluMist, Smokers, New and emerging tobacco products
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), Food and Drug Administration (FDA), Tobacco Centers of Regulatory Science (TCORS
- Study start
- Jun 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 lining fluid (ELF, collected with filter paper for cytokine analysis), 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, ELF, urine. Administer FluMist.
Day 1 (Tuesday): Obtain VS, NL, ELF, urine, NB #2
Day 2 (Wednesday): Obtain VS, NL, ELF, urine
Day 8 +/- 1 day (Monday-Wednesday): Obtain VS, NL, ELF, urine, NB #3
Day 21 +/- 7 days: Obtain VS, blood draw, collect completed smoking/exposure diary
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LAIV (FluMist) | – | Biological: LAIVAll subjects will receive a 0.2 mL dose of LAIV (FluMist) once during the study. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- 1. Nonsmokers 2. Cigarette smokers 3. Primarily e-cigarette smokers 4. Primarily hookah smokers 5. Primarily Little Cigar smokers
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (11 listed)
- Pregnancy or nursing;
- history of egg allergy;
- history of allergic rhinitis;
- aspirin therapy;
- asthma;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LAIVAlso: FluMistStandard dose of LAIV administered by a licensed health care providers. | Biological | LAIV (FluMist) |
Primary outcome
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
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.
6 secondary outcomes
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
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
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
Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for changes in mucus composition
Time frame: Basline, 7 weeks
Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for genomic signatures induced in epithelial cells
Time frame: Baseline, 7 weeks
Compare smoking (CS, EC, HS, and LCS) and nonsmoking groups (NS) for epigenomic signatures induced in epithelial cells
Time frame: Baseline, 7 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2018.
- Derived from this study: PubMed 33095645Rebuli 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ilona Jaspers, PhD principal investigator
University of North Carolina-Chapel Hill, Dept of Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Influenza, Human and Smoking, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02019745, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2018.