Woodsmoke Exposure, Influenza Infection, and Nasal Immunity

NCT06841913 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 24-18021R01ES036209-01
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effects of woodsmoke (WS) exposure on human nasal mucosal immune responses to viral infection. The study tests the hypotheses that WS exposure modifies biomarkers of nasal mucosal immune function, increases in Live Attenuated Influenza Virus (LAIV) -induced nasal symptoms, and reduces mucosal antibody production.

Conditions

Smoke Exposure; Influenza

Keywords

LAIV; Flumist; Influenza; Wood Smoke; Smoke; Fire

Outcome Measures

Primary Outcomes (6)

• Nasal Mucosal secretome (AUC)

  Analysis of the nasal mucosal secretome (secreted factors identified as responsive to WS and/or LAIV). Area under the curve (AUC) will be calculated for each proteomic profile. Descriptive statistics (means and standard deviations) will be computed for outcomes of interest (AUCs), assuming normal distribution as in previous studies.

  Day 0 to Day 7

• Gene Expression (AUC)

  Tissue-level gene expression (genes identified as responsive to WS and/or LAIV) and assessed for: tissue-level gene expression and untargeted metabolomic and proteomic profiles. Area under the curve (AUC) will be calculated for each gene profile. Descriptive statistics (means and standard deviations) will be computed for outcomes of interest (AUCs), assuming normal distribution as in previous studies.

  Day 0 to Day 7

• Virus Quantity (AUC)

  Virus quantity in nasal secretions

  Day 0 to Day 7

• Nasal Neutrophils (AUC)

  nasal secretion

  Day 0 to Day 7

• Nasal Viral Antibodies (AUC)

  virus-specific antibody levels in nasal secretions

  Day 0 to Day 7

• Blood Viral Antibodies (AUC)

  virus-specific antibody levels in blood

  Day 0 to Day 7

Secondary Outcomes (14)

• Peak Tissue gene expression

  Day 0 to Day 21

• Peak nasal secretome

  Day 0 to Day 21

• Peak Nasal Virus quantity

  Day 0 to day 21

• Peak nasal neutrophils

  Day 0 to Day 21

• Peak Nasal virus anti-bodies

  Day 0 to Day 21

Study Arms (4)

Wood smoke followed by LAIV

EXPERIMENTAL

Participants will receive LAIV after a 2 hour wood smoke exposure.

Biological: LAIV nasal vaccine is chosen as a model viral infection; Other: Wood smoke

Wood smoke followed by Placebo

ACTIVE COMPARATOR

Participants will receive a LAIV placebo after a 2 hour wood smoke exposure.

Other: Wood smoke; Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection

Clean Air followed by LAIV

ACTIVE COMPARATOR

Participants will receive LAIV after a 2 hour clean air exposure.

Biological: LAIV nasal vaccine is chosen as a model viral infection; Other: Placebo for Wood Smoke (clean Air Exposure)

Clean Air followed by Placebo

PLACEBO COMPARATOR

Participants will receive a LAIV placebo after a 2 hour clean air exposure.

Biological: Placebo for LAIV nasal vaccine is chosen as a model viral infection; Other: Placebo for Wood Smoke (clean Air Exposure)

Interventions

LAIV nasal vaccine is chosen as a model viral infection BIOLOGICAL

Inoculation with LAIV

Also known as: Live Attenuated Influenza Vaccine, Flumist

Clean Air followed by LAIV; Wood smoke followed by LAIV

Wood smoke OTHER

Wood smoke exposure concentrations at 500 ug/m3 for two hours.

Wood smoke followed by LAIV; Wood smoke followed by Placebo

Placebo for LAIV nasal vaccine is chosen as a model viral infection BIOLOGICAL

Placebo for LAIV inoculation. Nasal administration of normal saline.

Clean Air followed by Placebo; Wood smoke followed by Placebo

Placebo for Wood Smoke (clean Air Exposure) OTHER

Clean Air Exposure for 2 hours

Clean Air followed by LAIV; Clean Air followed by Placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Normal lung function,
• oxygen saturation of \>94%,
• normal blood pressure,
• no respiratory symptoms on history, no abnormalities on exam, normal pulmonary function testing,
• Years of age.

You may not qualify if:

• A history of significant chronic illnesses (to include diabetes, autoimmune diseases, immunodeficiency state, known ischemic heart disease, chronic respiratory diseases such as chronic obstructive pulmonary disease or asthma, hypertension)
• Positive pregnancy test within 48 hours of the time of challenge
• Use of any inhaled substance (for medical or recreational purposes).
• Nonsmokers must have been abstinent from smoking for the prior 12 months, having not smoked more than 1 pack over the course of the previous year.
• History of allergy to eggs
• Acute, non-chronic, medical conditions, including (but not limited to) pneumonia or bronchitis requiring antibiotics, febrile illnesses, flu-like symptoms must be totally resolved symptomatically for 3 weeks
• Expected exposure of subject to immunocompromised individuals (who can be infected by LAIV) for the 3 weeks following LAIV inoculation.
• Use of immunosuppressive drugs within the past 6 months.
• Previous Woodsmoke exposure \<3 weeks, which is considered to an appropriate washout period

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Environmental Health Sciences (NIEHS): collaborator

Study Sites (1)

Mary Ellen Jones

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; FluMist

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Meghan Rebuli, PhD

  UNC

  PRINCIPAL INVESTIGATOR

• Terry Noah, MD

  UNC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carole Robinette, MS

CONTACT

919 966-5638; carole_robinette@med.unc.edu

Chris Brooks

CONTACT

chris_brooks@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: This is a randomized, double-blinded study so packaging and labeling by IDS is such that both study participants and study personnel (lab techs) will be blinded to the treatment (either LAIV or placebo) given. Due to the smell of the WS it will not be possible to completely blind subjects or coordinators as to exposure. The contractor maintaining the woodsmoke exposure chamber add a small amount of woodsmoke into the chamber to minimize bias. The risk for bias is felt to be minimal because all of the study's primary and most of the secondary outcomes are laboratory assays for which the technicians performing the assays will be blinded as to subject group. Unblinding will occur at the conclusion of the study or earlier if needed for safety purposes and as dictated by the UNC IRB, study sponsor, and DSMB.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 25% of participants (N=100 total for the study) will undergo each of the following. Wood smoke followed by LAIV (N=25) Wood smoke followed by Placebo (N=25) Clean Air followed by LAIV (N=25) Clean Air followed by Placebo (N=25) Males and females will be equally enrolled into each of the above cohorts.

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: February 24, 2025
• Study Start: September 26, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication.
• Access Criteria: The investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Locations

US (1)