Woodsmoke Particulate + Prednisone

NCT03861390 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 18-2196
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Airway Inflammation

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Change in Number of Sputum Neutrophils

  Baseline, 4 and 24 hours post WSP exposure

• Change in Number of Sputum Eosinophils

  Baseline, 4 and 24 hours post WSP exposure

• Change in Percent Sputum Eosinophils

  Baseline, 4 and 24 hours post WSP exposure

• Change in IL-1b

  Baseline, 4 and 24 hours post WSP exposure

• Change in IL-6

  Baseline, 4 and 24 hours post WSP exposure

Other Outcomes (1)

• Mucociliary Clearance (MCC)

  4 hours post WSP exposure

Study Arms (2)

Prednisone, then Placebo

ACTIVE COMPARATOR

Participants will receive prednisone following WSP exposure. After a 4-week washout period, participants will receive placebo following WSP exposure.

Drug: 60 mg Prednisone; Drug: Placebo

Placebo, then Prednisone

PLACEBO COMPARATOR

Participants will receive placebo following WSP exposure. After a 4-week washout period, participants will receive prednisone following WSP exposure.

Drug: 60 mg Prednisone; Drug: Placebo

Interventions

60 mg Prednisone DRUG

Immediately following exit from the wood smoke chamber, subjects will receive 60 mg of prednisone per randomization schema

Placebo, then Prednisone; Prednisone, then Placebo

Placebo DRUG

Immediately following exit from the wood smoke chamber, subjects will receive a matching placebo to the 60 mg of prednisone per randomization schema

Placebo, then Prednisone; Prednisone, then Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• United States Department of Defense: collaborator

Study Sites (1)

Center for Environmental Medicine, Asthma and Lung Biology at UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (23)

• Pugh MJ, Jaramillo CA, Leung KW, Faverio P, Fleming N, Mortensen E, Amuan ME, Wang CP, Eapen B, Restrepo M, Morris MJ. Increasing Prevalence of Chronic Lung Disease in Veterans of the Wars in Iraq and Afghanistan. Mil Med. 2016 May;181(5):476-81. doi: 10.7205/MILMED-D-15-00035.

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• Ghio AJ, Soukup JM, Case M, Dailey LA, Richards J, Berntsen J, Devlin RB, Stone S, Rappold A. Exposure to wood smoke particles produces inflammation in healthy volunteers. Occup Environ Med. 2012 Mar;69(3):170-5. doi: 10.1136/oem.2011.065276. Epub 2011 Jun 30.

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  BACKGROUND

• Alexis NE, Zhou H, Lay JC, Harris B, Hernandez ML, Lu TS, Bromberg PA, Diaz-Sanchez D, Devlin RB, Kleeberger SR, Peden DB. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in human subjects. J Allergy Clin Immunol. 2009 Dec;124(6):1222-1228.e5. doi: 10.1016/j.jaci.2009.07.036.

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MeSH Terms

Interventions

Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Terry Noah, MD
• Organization: University of North Carolina at Chapel Hill

terry_noah@med.unc.edu

919-966-1055

Study Officials

• Terry Noah, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 4, 2019
• Study Start: March 22, 2019
• Primary Completion: May 12, 2023
• Study Completion: May 12, 2023
• Last Updated: June 25, 2024
• Results First Posted: May 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)