Novel Pulmonary Imaging of Lung Structure and Function in E-cigarette Smokers

E Cigarette Use Clinical Trial

Official title:

Novel Pulmonary Imaging of Lung Structure and Function in Symptomatic and Asymptomatic E-cigarette Smokers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04616313
• Other study ID #: ROB0048
• Status: Recruiting
• Start date: January 17, 2023
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Western University, Canada
• Contact: Grace E Parraga, PhD
• Phone: 519-931-5265
• Email: gparraga[@]robarts.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a longitudinal study of the long-term health impact of e-cigarette smoking on the lungs. Participants will be followed over a period of 5 years, and impacts of e-cigarette smoking on the lungs will be measured with magnetic resonance imaging (MRI) using hyperpolarized xenon-129 gas, pulmonary function tests, exercise capacity, computed tomography images and questionnaires.

Description:

This is a 5-year longitudinal study of the long-term lung health impact of e-cigarette smoking. Participants with a history of e-cigarette smoking age ≥ 16 years will be recruited from within 2 hours of London, ON through local family and tertiary care physicians, emergency departments and community and social media advertisements. Asymptomatic age and sex-matched participants who have never smoked e- or c-cigarettes will be recruited through community advertisement, media and social media. Participants must satisfy all inclusion and exclusion criteria in order to participate in the study. We will compare lung health of participants at baseline, 12 weeks, 24 weeks and 48 weeks, 3 years, 4 years and 5 years with an asymptomatic control group with no history of e-cigarette or c-cigarette use. The study will involve 6 in-person visits and 1 telephone call for a health update. All measurements will be made with at least 4 hours after the last cigarette and/or vape to provide a way to practically focus on chronic and not acute effects. Pulmonary function and imaging measurements will be made before and after bronchodilator administration.

At Visit 1, informed consent will be obtained before any study related assessments or procedures are performed. Eligibility criteria will be reviewed. Safety assessments including vital signs, pulmonary function testing, hematology, sputum sampling, exercise testing, and respiratory questionnaires will be completed.

Visit 2 will take place 12 weeks after visit 1 and will include vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, chest CT scan, exercise testing, and questionnaires.

Visit 3 will take place at 24 weeks and will involve a telephone call to update health information as well as questionnaires.

Visit 4 will take place at 48 weeks and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, hematology, blood chemistry, sputum analysis, exercise testing, and questionnaires.

Visit 5 will take place at year 3 and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, blood draw, sputum induction and analysis, exercise testing and questionnaires.

Visit 6 will take place at year 4 and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, blood draw, sputum induction and analysis, exercise testing and questionnaires.

Visit 7 will take place at year 5 and will involve vital signs, pre and post bronchodilator pulmonary function testing, pre and post bronchodilator MRI imaging, blood draw, sputum induction and analysis, exercise testing and questionnaires.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent must be directly obtained from legally competent participants before any study-related assessment is performed.

• Male and female participant age =16 years.

• Participant has recently started vaping, >1 and <5 years weekly use.

• 70 participants will be c-cigarette never users.

• 70 participants will be former or current c-cigarette users.

• 10 asymptomatic age and sex-matched healthy people who have never used e- or c-cigarettes will be controls.

Exclusion Criteria:

• Participants with contraindications for undergoing an MRI such as participants with MRI-sensitive implants, tattoos with MRI-sensitive dye and severe claustrophobia.

• Participant is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material.

• Participant unable to perform spirometry or plethysmography maneuvers.

Related Conditions & MeSH terms

• E Cigarette Use

Intervention

Diagnostic Test:
• Hyperpolarized Xenon-129 MRI of the lungs
Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
• Computed Tomography (CT)
Participants will undergo a CT scan of the thoracic cavity
• Pulmonary Function Tests (PFT)
Participants will have their lung function evaluated using PFT
• Cardiopulmonary exercise testing (CPET)
Participants will perform cardiopulmonary exercise testing as a measure of exercise capacity
• Sputum analysis
Participants will provide a sputum sample that will be analysed for eosinophils
• Blood analysis
Participants will have their blood drawn and analysed for eosinophil count.

Other:
• Questionnaires
Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.

Locations

Country	Name	City	State
Canada	Robarts Research Institute; The University of Western Ontario; London Health Sciences Centre	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Western University, Canada	London Health Sciences Centre

Country where clinical trial is conducted

Canada, 

References & Publications (19)

Cho JH, Paik SY. Association between Electronic Cigarette Use and Asthma among High School Students in South Korea. PLoS One. 2016 Mar 4;11(3):e0151022. doi: 10.1371/journal.pone.0151022. eCollection 2016. — View Citation

Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB. — View Citation

Davidson K, Brancato A, Heetderks P, Mansour W, Matheis E, Nario M, Rajagopalan S, Underhill B, Wininger J, Fox D. Outbreak of Electronic-Cigarette-Associated Acute Lipoid Pneumonia - North Carolina, July-August 2019. MMWR Morb Mortal Wkly Rep. 2019 Sep 13;68(36):784-786. doi: 10.15585/mmwr.mm6836e1. — View Citation

Henry TS, Kanne JP, Kligerman SJ. Imaging of Vaping-Associated Lung Disease. N Engl J Med. 2019 Oct 10;381(15):1486-1487. doi: 10.1056/NEJMc1911995. Epub 2019 Sep 6. No abstract available. — View Citation

Hua M, Alfi M, Talbot P. Health-related effects reported by electronic cigarette users in online forums. J Med Internet Res. 2013 Apr 8;15(4):e59. doi: 10.2196/jmir.2324. — View Citation

Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509. — View Citation

Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7. doi: 10.1164/ajrccm/145.6.1321. — View Citation

Kirby M, Heydarian M, Svenningsen S, Wheatley A, McCormack DG, Etemad-Rezai R, Parraga G. Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation. Acad Radiol. 2012 Feb;19(2):141-52. doi: 10.1016/j.acra.2011.10.007. Epub 2011 Nov 21. — View Citation

Landman ST, Dhaliwal I, Mackenzie CA, Martinu T, Steel A, Bosma KJ. Life-threatening bronchiolitis related to electronic cigarette use in a Canadian youth. CMAJ. 2019 Dec 2;191(48):E1321-E1331. doi: 10.1503/cmaj.191402. Epub 2019 Nov 20. — View Citation

Layden JE, Ghinai I, Pray I, Kimball A, Layer M, Tenforde MW, Navon L, Hoots B, Salvatore PP, Elderbrook M, Haupt T, Kanne J, Patel MT, Saathoff-Huber L, King BA, Schier JG, Mikosz CA, Meiman J. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med. 2020 Mar 5;382(10):903-916. doi: 10.1056/NEJMoa1911614. Epub 2019 Sep 6. — View Citation

Maddock SD, Cirulis MM, Callahan SJ, Keenan LM, Pirozzi CS, Raman SM, Aberegg SK. Pulmonary Lipid-Laden Macrophages and Vaping. N Engl J Med. 2019 Oct 10;381(15):1488-1489. doi: 10.1056/NEJMc1912038. Epub 2019 Sep 6. No abstract available. — View Citation

McConnell R, Barrington-Trimis JL, Wang K, Urman R, Hong H, Unger J, Samet J, Leventhal A, Berhane K. Electronic Cigarette Use and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1043-1049. doi: 10.1164/rccm.201604-0804OC. — View Citation

McGavin CR, Artvinli M, Naoe H, McHardy GJ. Dyspnoea, disability, and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J. 1978 Jul 22;2(6132):241-3. doi: 10.1136/bmj.2.6132.241. — View Citation

Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available. — View Citation

Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. doi: 10.1183/09031936.03.00089403. — View Citation

Owrangi AM, Etemad-Rezai R, McCormack DG, Cunningham IA, Parraga G. Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers. Acad Radiol. 2013 May;20(5):537-45. doi: 10.1016/j.acra.2012.11.010. — View Citation

Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17. doi: 10.1164/ajrccm.154.2.8756799. — View Citation

Schweitzer RJ, Wills TA, Tam E, Pagano I, Choi K. E-cigarette use and asthma in a multiethnic sample of adolescents. Prev Med. 2017 Dec;105:226-231. doi: 10.1016/j.ypmed.2017.09.023. Epub 2017 Sep 28. — View Citation

Wang MP, Ho SY, Leung LT, Lam TH. Electronic Cigarette Use and Respiratory Symptoms in Chinese Adolescents in Hong Kong. JAMA Pediatr. 2016 Jan;170(1):89-91. doi: 10.1001/jamapediatrics.2015.3024. No abstract available. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report pulmonary imaging abnormalities.	Measured using 129-Xe MRI	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report pulmonary imaging abnormalities.	Measured using computed tomography imaging	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FEV1.	Measured using forced expiratory volume in one second (FEV1)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FVC.	Measured using forced vital capacity (FVC)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by TLC.	Measured using total lung capacity (TLC)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FRC.	Measured using functional residual capacity (FRC)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by RV.	Measured using residual volume (RV)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FOT.	Measured using forced oscillation technique (FOT)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by LCI.	Measured using lung clearance index (LCI)	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by FeNO.	Measured using Fractional Exhaled Nitric Oxide (FeNO).	12 weeks following enrollment
Primary	Determine if e-cigarette users who did not require hospitalization, nor used c-cigarettes report respiratory symptoms or abnormal pulmonary function measured by exercise capacity	Exercise capacity measured by cardio-pulmonary exercise testing (CPET)	12 weeks following enrollment
Secondary	Differences in airways between e-cigarette-only smokers and both e-cigarette and c-cigarette smokers.	Measured using 129-Xe MRI	5 years
Secondary	Differences in airways between e-cigarette-only smokers and never smokers.	Measured using 129-Xe MRI	5 years
Secondary	Differences in parenchyma between e-cigarette-only smokers and both e-cigarette and c-cigarette smokers.	Measured using 129-Xe MRI	5 years
Secondary	Differences in parenchyma between e-cigarette-only smokers and never smokers.	Measured using 129-Xe MRI	5 years
Secondary	Changes in airways of e-cigarette smokers over time.	Measured using Xenon-129 (129-Xe) MRI	5 years
Secondary	Changes in parenchyma of e-cigarette smokers over time.	Measured using Xenon-129 (129-Xe) MRI	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by FEV1.	Measured using forced expiratory volume in one second (FEV1).	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by FVC.	Measured using forced vital capacity (FVC)	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by TLC.	Measured using total lung capacity (TLC)	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by FRC.	Measured using functional residual capacity (FRC)	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by RV.	Measured using residual volume (RV)	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by FOT.	Measured using forced oscillation technique (FOT).	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by LCI.	Measured using lung clearance index (LCI)	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by FeNO.	Measured using Fractional Exhaled Nitric Oxide (FeNO)	5 years
Secondary	Changes in lung function of e-cigarette smokers over time as measured by exercise capacity.	Exercise capacity measured by cardio-pulmonary exercise testing (CPET)	5 years
Secondary	Changes in lung health of e-cigarette smokers over time as measured by the mMRC dyspnea scale questionnaire.	Measured using the modified medical research council (mMRC) dyspnea scale	5 years
Secondary	Changes in lung health of e-cigarette smokers over time as measured by SGRQ.	Measured using the St. George's respiratory questionnaire (SGRQ)	5 years
Secondary	Changes in lung health of e-cigarette smokers over time as measured by CAT.	Measured using the COPD assessment test (CAT)	5 years
Secondary	Changes in lung health of e-cigarette smokers over time as measured by IPAQ.	Measured using the International Physical Activity Questionnaire (IPAQ).	5 years