Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Woodsmoke Particulate + Prednisone (Smokisone)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03861390
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : January 5, 2022
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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.

Condition or disease Intervention/treatment Phase
Airway Inflammation Drug: 60 mg Prednisone Drug: Placebo Phase 1 Phase 2

Detailed Description:

Military deployment is associated with exposure to novel particulate matter (PM), such as from burn pits, aeroallergens, and increased cigarette consumption. War fighters exposed to these inhalational exposures exhibit immediate and chronic respiratory morbidity. For example, military service personnel surveyed in both the Republic of Korea (ROK) and Kabul, Afghanistan reported a general increase in respiratory morbidity, including asthma and chronic bronchitis, associated with their deployment. Air contaminants in the ROK were characterized by elevated levels of both PM 0.5-2.5 and PM 2.5-10. Similarly, exposures in Kabul were characterized by multiple airborne PM exposures, including those from burn pits. Burn pit PM includes metals, bioaerosols, organic by-products, and biomass combustion particles. These findings indicate that inhaled PM is a likely cause of respiratory morbidity in the field.

Inflammation is a key initial response to inhaled particulates. Wood smoke particles (WSP) serve as a model agent to study PM-induced bronchitis. WSP inhalation generates reactive oxidant (and nitrosative) species which cause local injury of airway epithelial cells and release of damage-associated molecular patterns (DAMPs) that activate toll-like receptors (TLR) and Interleukin (IL)-1-mediated innate immune responses by resident airway macrophages. Contamination of PM with bioaerosols, which contain lipopolysaccharide (LPS), also activates innate immune responses through toll-like receptor 4 (TLR4) activation of resident airway macrophages. These complementary processes result in recruitment of neutrophils (PMN), which mediate luminal airway inflammation with release of toxic mediators such as neutrophil elastase and myeloperoxidase that promote acute and chronic bronchitis.

Therefore, mitigation of PM-induced airway neutrophilic inflammation should be a key focus in order to reduce the respiratory morbidity of military personnel. The researchers have studied a number of pro-inflammatory inhaled agents, such as nebulized LPS, ozone (O3), and WSP, as models of acute neutrophilic bronchitis against which to test a number of therapeutic agents. To this effect, the researchers have reported that inhaled fluticasone inhibits O3-induced and LPS-induced neutrophilic inflammation, and that parenteral anakinra and oral gamma-tocopherol inhibit neutrophilic responses to inhaled LPS. In this study, the researchers will evaluate the efficacy of oral prednisone, a readily available anti-inflammatory medication commonly used in airway inflammatory diseases, in mitigating WSP-induced airway inflammation.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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).
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase I/II Randomized, Double-blind, Placebo-controlled Cross-over Study of Prednisone on Airway Inflammatory Response to Inhaled Wood Smoke.
Actual Study Start Date : March 22, 2019
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids
Drug Information available for: Prednisone

Arm Intervention/treatment
Active Comparator: Prednisone, then Placebo Drug: 60 mg Prednisone
Immediately following exit from the wood smoke chamber, subjects will receive 60 mg of prednisone per randomization schema

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

Placebo Comparator: Placebo, then Prednisone Drug: 60 mg Prednisone
Immediately following exit from the wood smoke chamber, subjects will receive 60 mg of prednisone per randomization schema

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




Primary Outcome Measures :
  1. change in sputum % neutrophils with WSP exposure [ Time Frame: (6 hours post WSP - pre WSP [Prednisone]) vs (6 hours post WSP - pre WSP [Placebo]) ]
    comparing the change in sputum % neutrophils 6 hours post WSP exposure with Prednisone versus placebo


Secondary Outcome Measures :
  1. change in sputum % neutrophils with WSP at 24 hours [ Time Frame: (24 hours post WSP - pre WSP [Prednisone]) vs (24 hours post WSP - pre WSP [Placebo]) ]
    comparing the change in sputum % neutrophils 24 hours post WSP exposure with Prednisone versus placebo

  2. change in neutrophils/mg with WSP at 6 and 24 hours [ Time Frame: (6 hours post WSP - pre WSP [Prednisone]) vs (6 hours post WSP - pre WSP [Placebo]) and (24 hours post WSP - pre WSP [Prednisone]) vs (24 hours post WSP - pre WSP [Placebo]) ]
    comparing the change in neutrophils/mg 6 and 24 hours post WSP exposure with Prednisone versus Placebo

  3. Mucociliary Clearance (MCC) Associated With Inhaled Wood Smoke Exposure as Affected by Prednisone [ Time Frame: 4 hours post WSP with Prednisone vs 4 hours post WSP with Placebo ]
    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 and compare Prednisone vs Placebo.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 IRB# 15-1775).

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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03861390


Contacts
Layout table for location contacts
Contact: Martha Almond 9199660759 martha_almond@med.unc.edu
Contact: Carole Robinette, MS 919-966-5638

Locations
Layout table for location information
United States, North Carolina
Center for Environmental Medicine, Asthma and Lung Biology at UNC Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Carole Robinette    919-966-5638    carole_robinette@med.unc.edu   
Sponsors and Collaborators
University of North Carolina, Chapel Hill
United States Department of Defense
Investigators
Layout table for investigator information
Principal Investigator: Terry Noah, MD University of North Carolina, Chapel Hill
Publications:
Jones B, and Kenward, M.G. . Design and analysis of cross-over trials. Third ed: CRC Press; 2015

Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03861390    
Other Study ID Numbers: 18-2196
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: January 5, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Inflammation
Pathologic Processes
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents