Airway Inflammation Clinical Trial
— SmokeysalOfficial title:
Phase I/II Randomized Cross-over Study of Hypertonic Saline on Airway Inflammatory Response to Inhaled Wood Smoke
Verified date | April 2023 |
Source | University of North Carolina, Chapel Hill |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Deployment of military personnel has been associated with increased respiratory illness likely due, in part, to inhalation of unusual particulate matter (PM), such as from burn pits. Inflammation is a key initial response to inhaled particulates. The investigator has developed a protocol using inhaled wood smoke particles (WSP) as a way to study PM-induced airway inflammation. Exposure to wood smoke particles causes symptoms, even in healthy people, such as eye irritation, cough, shortness of breath, and increased mucous production. The purpose of this research study is to see if a single treatment of inhaled hypertonic saline (HS) can diminish this PM-induced airway inflammation by rapidly clearing the WSP inhaled particles from airway surfaces. The exposure will be 500 ug/m³ of WSP for 2 hours, with intermittent exercise on a bicycle and rest. The wood is burned in a typical wood stove and piped into the chamber.
Status | Enrolling by invitation |
Enrollment | 14 |
Est. completion date | September 2024 |
Est. primary completion date | September 1, 2024 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 45 Years |
Eligibility | Inclusion Criteria: - Age 18-45 years, inclusive, of both genders - Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy - No history of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician-diagnosed asthma. - forced expiratory volume at one second (FEV1) of at least 80% of predicted and FEV1/forced vital capacity (FVC) ratio of >0.70. - Oxygen saturation of >93% - Ability to provide an induced sputum sample. - Subject must demonstrate a >10% increase in sputum %PMNs 6 hours following inhaled WSP exposure, when compared to baseline sputum (to be completed in a separate protocol IRB# 15-1775). - Proof of vaccination to Covid based on public health guidelines at time of inclusion Exclusion Criteria: - Clinical contraindications: - Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections/immunodeficiency. - Viral upper respiratory tract infection within 4 weeks of challenge. - Any acute infection requiring antibiotics within 4 weeks of exposure or fever of unknown origin within 4 weeks of challenge. - Abnormal physical findings at the baseline visit, including but not limited to abnormalities on auscultation, temperature of 37.8° C, Systolic BP > 150mm Hg or < 85 mm Hg; or Diastolic BP > 90 mm Hg or < 50 mm Hg, or pulse oximetry saturation reading less than 93%. - Physician diagnosis of asthma - If there is a history of allergic rhinitis, subjects must be asymptomatic of allergic rhinitis at the time of study enrollment. - Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements. - Medications which may impact the results of the WSP exposure, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents) - Cigarette smoking > 1 pack per month - Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms). - Use of immunosuppressive or anticoagulant medications including routine use of NSAIDS. Oral contraceptives are acceptable, as are antidepressants and other medications may be permitted if, in the opinion of the investigator, the medication will not interfere with the study procedures or compromise safety and if the dosage has been stable for 1 month. - Orthopedic injuries or impediments that would preclude bicycle or treadmill exercise. - Inability to avoid NSAIDS, Multivitamins, Vitamin C or E or herbal supplements. - Allergy/sensitivity to study drugs or their formulations - Positive Covid test in the past 90 days. - Pregnant/lactating women and children (< 18 years as this is age of majority in North Carolina) will also be excluded since the risks associated with WSP exposure to the fetus or child, respectively, are unknown and cannot be justified for this non-therapeutic protocol. Individuals over 45 years of age will not be included due to the increased possibility of co-morbidities and need for prohibited medications. - Inability or unwillingness of a participant to give written informed consent |
Country | Name | City | State |
---|---|---|---|
United States | Center for Environmental Medicine, Asthma and Lung Biology at UNC Chapel Hill | Chapel Hill | North Carolina |
Lead Sponsor | Collaborator |
---|---|
University of North Carolina, Chapel Hill | United States Department of Defense |
United States,
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* Note: There are 23 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Mucociliary Clearance (MCC) | 4 hours post WSP exposure, the MCC is done. A whole lung region of interest (ROI) bordering the right lung is used to estimate (by computer analysis) whole lung retention of inhaled radiolabeled particles. Labeled particle counts are measured over a 2 hour period to determine the fraction of initial particle counts remaining. From this data, the investigators will determine the percentage of labeled particles cleared from the lung during the 2 hour observation period. | 4 hours post WSP exposure] | |
Primary | Change From Baseline to 4 Hours in Sputum Percent Neutrophils | Change in sputum percent neutrophils from baseline to 4 hours post WSP exposure | Baseline, 4 hours post WSP exposure | |
Primary | Change From Baseline to 24 Hours in Sputum Percent Neutrophils | Change in sputum percent neutrophils from baseline to 24 hours post WSP exposure | Baseline, 24 hours post WSP exposure | |
Secondary | Change in Number of Sputum Neutrophils | Neutrophil numbers/mg measured at 4 and 24 hours post-WSP exposure. | up to 24 hours | |
Secondary | Change in Number of Sputum Eosinophils | Eosinophil numbers/mg measured at 4 and 24 hours post-WSP exposure | up to 24 hours | |
Secondary | Change in Percent Sputum Eosinophils | Percent eosinophils measured at 4 and 24 hours post WSP exposure | up to 24 hours | |
Secondary | Change in IL-1b | IL-1b via Mesoscale platform (pg/mL) at 4 and 24 hours post WSP exposure | up to 24 hours | |
Secondary | Change in IL-6 | IL-6 via Mesoscale platform (pg/mL) at 4 and 24 hours post WSP exposure | up to 24 hours | |
Secondary | Change in IL-8 | IL-8 via Mesoscale platform (pg/mL) at 4 and 24 hours post WSP exposure | up to 24 hours | |
Secondary | Change in TNFa | TNFa via Mesoscale platform (pg/mL) at 4 and 24 hours post WSP exposure | up to 24 hours |
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