Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02743468
Other study ID # 160096
Secondary ID 16-E-0096
Status Completed
Phase
First received
Last updated
Start date January 8, 2019
Est. completion date September 21, 2023

Study information

Verified date September 25, 2023
Source National Institutes of Health Clinical Center (CC)
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Background: Respiratory diseases affect more than 1 billion people worldwide. They are a growing public health concern. The lungs are constantly exposed to environmental factors such as dust, fumes, microbes, and pollutants. But much is still not known about how these pollutants lead to respiratory illnesses. Researchers want to collect samples from lungs and blood to see how genetics and environmental pollutants affect cellular responses or functioning. Objectives: To study how cytochrome P450 epoxygenase pathway enzymes affect macrophage function in the lungs and inflammatory responses. Eligibility: Adults ages 18 65 who can have a bronchoscopy. Design: All study visits will take place at the NIEHS Clinical Research Unit in Research Triangle Park, NC. At study visit 1, participants will be screened with medical history and physical exam. They will have blood and urine tests. They will take tests that measure their lung function. They will answer questionnaires. Before the visit, they will be given a list of medicines they cannot take. They also must not have caffeine on the day of their visit. The visit will last about 3 hours. At study visit 2, participants will give blood samples. They will undergo bronchoscopy. For this, they will get an intravenous line in a vein to get sedatives. Their airways will be numbed. Cells will be collected from their lungs. They will fast for 8 hours before the visit. They must have someone else drive them home from the visit. The visit will last about 3-4 hours. Participants will get a follow-up phone call about 1 day after study visit 2.


Description:

This is a prospective, cross-sectional study designed to provide a consistent method for obtaining biological samples and respiratory health-related information from participants for use in research that evaluates lung function (e.g., responses to environmental agents such as air pollution particles, engineered nanomaterials, or immune ligands; the role of genetics on cellular responses or functioning). Study participants will be adult volunteers, ages 18-65 (inclusive), who meet eligibility criteria to undergo bronchoscopy. Potential participants will be prescreened and scheduled for a final eligibility visit that will include medical history review, vital signs, physical examination, blood draw, and pulmonary function tests. After eligibility is confirmed, the participant will be scheduled for biological sample collections, which will include a blood draw and bronchoscopy. The objective of this protocol is to investigate the role of cytochrome P450 (CYP) epoxygenase pathway enzymes, including the soluble epoxide hydrolase (sEH; encoded by EPHX2) and CYP2J2 proteins, in macrophage function and inflammatory responses. The primary outcome measure will evaluate macrophage phagocytosis in an ex vivo assay, comparing groups of individuals with and without EPHX2 and CYP2J2 polymorphisms of interest. Secondary outcomes will include evaluations of ex vivo gene expression of inflammatory receptors and cytokines in stimulated macrophages (alveolar and peripheral blood monocyte-derived), assessment of the lower airway microbiome from bronchoalveolar lavage (BAL) fluid, and measurement of eicosanoids and cytokines in serum and BAL fluid.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date September 21, 2023
Est. primary completion date December 18, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility - INCLUSION CRITERIA: 1. Age 18 to 65 years, inclusive (males and females) 2. Able to travel to the NIEHS CRU for required study visits 3. Able to present a valid government-issued form of identification for entry to the NIEHS campus 4. Able to fast for 8 hours prior to the visit where bronchoscopy occurs 5. Has a responsible party who is willing and able to attend Visit 2 and drive the participant away from the CRU after completion of Visit 2, if the participant elects to undergo conscious sedation 6. Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - Wild type with respect to EPHX2 K55R, EPHX2 R287Q, and CYP2J2*7; or - Homozygous for EPHX2 K55R (wild type for the other SNPs); or - Homozygous for EPHX2 R287Q (wild type for the other SNPs); or - Homozygous for CYP2J2*7 (wild type for the other SNPs) EXCLUSION CRITERIA: 1. Current pregnancy or lactation, as medications used during the bronchoscopy can be excreted in the breast milk of lactating mothers 2. Current smoker or significant second-hand smoke exposure (defined by urine cotinine >200 ng/mL at screening) 3. Post-bronchodilator FEV1 < 70% of predicted 4. For asthmatics, any indication of moderate or severe asthma such as: - Physician-directed emergency treatment for an asthma exacerbation within the preceding 12 months - Any use of systemic steroid therapy during the last year or continuous use of inhaled steroids over a period of 1 month or longer during the past 6 months - Regular use of cromolyn (except for prophylaxis of exercise induced bronchospasm) or any use of leukotriene inhibitors (Montelukast or Zafirlukast) within the past month - Symptoms including: - Night-time symptoms of cough or wheeze greater than 1x/week - Exacerbations of asthma more than 2x/week - Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) 5. Bleeding disorders or regular use of aspirin or other non-steroidal anti-inflammatory drugs (which inhibit platelet function) or other drugs that prolong bleeding time such as warfarin, heparin or derivatives, or clopidogrel and related ADP inhibitors 6. Sickle cell disease or GP6 deficiency 7. Facial deformity or major facial surgery 8. Asthma exacerbation or respiratory infection 4 weeks prior to study visit 9. Allergy or history of adverse reactions to lidocaine, midazolam, or fentanyl 10. Vital signs (temperature, blood pressure, pulse rate) that are outside of the established CRU limits 11. Body weight <50 kg (<110 lbs) 12. The following abnormal clinical laboratory values (obtained during Visit 1 assessment): - Platelet count <100,000 per L - White blood cells count <3000 per L - Absolute neutrophil count <1000 per L - Hematocrit <35% for both female and male - PT/INR and PTT based on reference laboratory established reference ranges - Serum creatinine >1.4 mg/dL 13. Any condition that, in the investigator's opinion, places the participant at undue risk for complications associated with required study procedures. 14. Use of the medication colchicine (commonly used to treat gout attacks) in the past 2 weeks. Volunteers meeting any of the below temporary exclusions may enroll in the study, but may not undergo the bronchoscopy procedure within the time frames specified for each below temporary exclusion. If any of the following conditions are met, the bronchoscopy will be rescheduled such that none of these temporary exclusions apply: Temp. EXCL 1. An asthma exacerbation requiring increased asthma medications for more than 1 day (and other than exercise-induced asthma) within 1 month of bronchoscopy Temp. EXCL 2. Viral upper respiratory tract infection or any acute infection requiring antibiotics within 4 weeks of bronchoscopy Temp. EXCL 3. Use of anti-inflammatory medications (including over-the-counter preparations) during the 48 hours prior to the bronchoscopy and aspirin during the 14 days prior to bronchoscopy. Temp. EXCL 4. Any food or fluids for 8 hours prior to the bronchoscopy

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
United States NIEHS, Research Triangle Park Research Triangle Park North Carolina

Sponsors (1)

Lead Sponsor Collaborator
National Institute of Environmental Health Sciences (NIEHS)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary The primary outcome measure will evaluate macrophage phagocytosis of fluorescein isothiocyanate (FITC)-labeled beads and bacteria (Streptococcus pneumoniae) in an ex vivo assay, comparing alveolar macrophages from groups of individuals with and ... The primary outcome measure will evaluate macrophage phagocytosis of fluorescein isothiocyanate (FITC)-labeled beads and bacteria (Streptococcus pneumoniae) in an ex vivo assay, comparing alveolar macrophages from groups of individuals with and without EPHX2 and CYP2J2 polymorphisms of interest. Cross-sectional
See also
  Status Clinical Trial Phase
Terminated NCT03309358 - A Study of the Safety and Tolerability of Inhaled SNSP113 in Healthy Subjects and Subjects With Stable Cystic Fibrosis Phase 1
Recruiting NCT04115514 - Treatment of ARDS With Instilled T3 Phase 2
Completed NCT02277002 - Commuter Air Pollution Intervention Study N/A
Completed NCT05260827 - The Effects of Heated Tobacco Products Use on Lung Function and Volatile Organic Compounds in Exhaled Air N/A
Completed NCT04606069 - Treat COVID-19 Patients With Regadenoson Phase 1/Phase 2
Completed NCT02151552 - Assessing NOS Uptake With PET Imaging in Lung Inflammation Early Phase 1
Recruiting NCT05854563 - Cough Capture as a Portal Into the Lung
Active, not recruiting NCT05752019 - TAAI Erasmus Research Initiative to Fight CF: Monitoring Inflammation in CF Lung Disease Into a New Era
Completed NCT00741013 - Quantifying Airway Inflammation With Radiologic Tests Phase 0
Completed NCT01174056 - Evaluation of Rosiglitazone Anti-inflammatory Effect With FDG-PET Imaging Phase 0
Recruiting NCT04755478 - LUS to Assess Lung Injury After Lung Lobectomy
Completed NCT03905837 - Impact of Lidocaine Administration on Postoperative Complications During Lung Resection Surgery Phase 4
Recruiting NCT03312712 - Validation of the Analysis Methodology Behind the Use of Quantitative 18F-FDG PET/CT to Assess Lung Inflammation
Recruiting NCT03492762 - PET Imaging CCR2 in Lung Inflammation Early Phase 1
Recruiting NCT04677309 - LUS to Assess Lung Injury After Lung Resection
Terminated NCT02848586 - Effects of E-cigarettes (ECIGs) on Pulmonary Inflammation and Behavior in HIV Infected Smokers N/A
Enrolling by invitation NCT04781153 - Bergen Oral Respiratory Intervention Study N/A
Withdrawn NCT04782700 - P-Co-Li (Pulmonary Covid-19 Study) N/A