Phase I/II Randomized, Double-blind, Placebo-controlled Cross-over Study of Prednisone on Airway Inflammatory Response to Inhaled Wood Smoke

18-2196

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 researchers have 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 an oral steroid treatment can reduce the airway inflammation caused by the inhaled WSP. The exposure will be 500 µg/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.

2019-03-22

2023-05-12

2023-05-12

Completed

Early phase I

12

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) ≥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 # 15-1775). * Proof of vaccination to COVID-19. 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-19 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': 'The randomization schedule will be generated by using permuted block randomization with a block size of 4 (2 prednisone, 2 placebo for the first treatment period of the protocol).', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 12, 'type': 'ACTUAL'}}

2024-05-23