A single-blinded, single-centre, controlled study in healthy adult smokers to identify the effects of a reduced toxicant prototype cigarette on biomarkers of exposure and of biological effect versus commercial cigarettes

BMC Public Health

Ingo Meyer¹  Don Graff²  Alison Eldridge³  Nik Newland³  Christopher J Shepperd³ 

[1] MPS Hamburg GmbH, Kieler Strasse 99-105, Hamburg 22769, Germany;Celerion, 621 Rose St, Lincoln, NE 68502, USA;British American Tobacco, Group Research and Development, Regents Park Road, Southampton SO15 8TL, UK

关键词: Smoking;    MRTP;    Modified risk tobacco product;    PREP;    Potential reduced-exposure product;    Reduced toxicant prototype cigarettes;    Tobacco smoke toxicants;    Biomarker of biological effect;    Biomarker of exposure;   

Others  :  1161992
DOI  :  10.1186/1471-2458-13-690

 received in 2012-12-21, accepted in 2013-07-11,  发布年份 2013

【 摘 要 】

Background

Despite universal acceptance that smoking is harmful, a substantial number of adults continue to smoke. The development of potential reduced exposure products (more recently termed modified risk tobacco products) has been suggested as a way to reduce the risks of tobacco smoking. This trial is designed to investigate whether changes in toxicant exposure after switching from a commercial to reduced toxicant prototype (RTP) cigarette (7 mg International Organisation for Standardisation (ISO) tar yield) can be assessed by measurement of biomarkers and other factors. The primary objective is to descriptively assess changes in selected biomarkers of exposure (BoE) and biomarkers of biological effect (BoBE) within participants and within and between groups after switching. Secondary objectives are to assess similarly changes in other biomarkers, quality of life, smoking behaviours, physiological measures, mouth-level exposure to toxicants and sensory perception.

Methods/design

This trial will assess current smokers, ex-smokers and never-smokers in a single-centre single-blind, controlled clinical trial with a forced-switching design and in-clinic (residential) and ambulatory (non-residential) periods. Smokers will be aged 23–55 years (minimum legal smoking age plus 5 years) and non-smokers 28–55 years (minimum legal smoking age plus 5 years, plus minimum 5 years since last smoked). Smokers will be allowed to smoke freely at all times. We will assess changes in selected BoE and BoBE and effective dose in urine and blood after switching. Creatinine concentrations in serum, creatinine clearance in urine, cotinine concentration in saliva, diaries and collection of spent cigarette filters will be used to assess compliance with the study protocol. Mouth-level exposure to toxins will be assessed by filter analysis.

Discussion

Data from this study are expected to improve scientific understanding of the effects of RTP cigarettes on BoE and BoBE, and give insights into study design for clinical assessment of potential MRTPs.

Trial registration

The study was registered in the Current Controlled Trials database under the reference ISRCTN81286286.

【 授权许可】

   
2013 Shepperd et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]MacKay J: The Tobacco Atlas. Geneva: World Health Organization; 2006.
• [2]Stratton K, Shetty P, Wallace R, Bondurant S: Clearing the smoke: assessing the science base for tobacco harm reduction. Washington, DC: National Academy Press; 2001.
• [3]Hatsukami DK, Hanson K, Briggs A, Parascandola M, Genkinger J, O’Connor RJ, Shields PG: Clinical trials methods for evaluation of potential reduced exposure products. Cancer Epidemiol Biomarkers Prev 2009, 18:143-195.
• [4]Burns DM, Dybing E, Gray N, Hecht S, Anderson C, Sanner T, O'Connor R, Djordjevic M, Dresler C, Hainaut P, Jarvis M, Opperhuizen A, Straif K: Mandated lowering of toxicants in cigarette smoke: a description of the WHO TobReg proposal. Tob Control 2008, 17:132-141.
• [5]Liu C, Degrandpre Y, Porter A, et al.: The use of a novel tobacco treatment process to reduce toxicant yields in cigarette smoke. Food Chem Toxicol 2011, 49(8):1904-1917.
• [6]McAdam K, Gregg EO, Liu C, et al.: The use of a novel tobacco-substitute sheet and smoke dilution to reduce toxicant yields in cigarette smoke. Food Chem Toxicol 2011, 49:1684-1696.
• [7]Branton PJ, McAdam KG, Duke MG, et al.: Use of classical adsorbtion theory to understand the dynamic filtration of volatile toxicants in cigarette smoke by active carbons. Absorption Sci Technol 2011, 29:117-138.
• [8]Branton PJ, McAdam KG, Winter DB, et al.: Reduction of aldehydes and hydrogen cyanide yields in mainstream cigarette smoke using and amine-functionalised ion exchange resin. Chem Cent J 2011, 5:15. BioMed Central Full Text
• [9]Shepperd CJ, Eldridge AC, Mariner DC, McEwan M, Errington G, Dixon M: A study to estimate and correlate cigarette smoke exposure in smokers in Germany as determined by filter analysis and biomarkers of exposure. Regul Tox Pharmacol 2009, 55:97-109.
• [10]Shepperd CJ, Eldridge AC, Errington G, Dixon M: A study to evaluate the effect on Mouth Level Exposure and biomarkers of exposure estimates of cigarette smoke exposure following a forced switch to a lower ISO tar yield cigarette. Regul Tox Pharmacol 2011, 61(3 Suppl):S13-S24.
• [11]Morin A, et al.: Estimation and correlation of cigarette smoke exposure in Canadian smokers as determined by filter analysis and biomarkers of exposure. Regul Tox Pharmacol 2011, 61(3 Suppl):S3-12.
• [12]McAdam K, Gregg EO, Bevan M, Dittrich D, Hemsley S, Liu C, Proctor CJ: Design and chemical evaluation of prototype reduced machine-yield cigarettes. Regul Tox Pharmacol 2012, 62:138-150.
• [13]Shepperd CJ, Eldridge AC, Camacho OM, McAdam K, Proctor CJ, Meyer I: Changes in levels of biomarkers of exposure observed in a controlled study of smokers switched from conventional to reduced toxicant prototype cigarettes. Regul Tox Pharmacol 2013, 66(1):147-162.
• [14]Andreoli C, Gregg EO, Puntoni R, Gobbi V, Nunziata A, Bassi A: Cross-sectional study of biomarkers of exposure and biological effect on monozygotic twins discordant for smoking. Clin Chem Lab Med 2011, 49:137-145.
• [15]Schettgen T, Broding HC, Angerer J, Drexler H: Hemoglobin adducts of ethylene oxide, propylene oxide, acrylonitrile and acrylamide-biomarkers in occupational and environmental medicine. Toxicol Lett 2002, 134:65-70.
• [16]Seyler TH, Reyes LR, Bernert JT: Analysis of 4-aminobiphenyl hemoglobin adducts in smokers and nonsmokers by pseudo capillary on-column gas chromatography-tandem mass spectrometry. J Anal Toxicol 2010, 34:304-311.
• [17]ICH Harmonized Tripartite Guideline: Guideline for Good Clinical Practice. 1996. E6 (R1). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1_Guideline.pdf webcite
• [18]World Medical Association, Declaration of Helsinki: ethical principles for medical research involving human subjects. http://www.wma.net/en/30publications/10policies/b3/17c.pdf webcite
• [19]Flockhart DA: Drug Interactions: Cytochrome P450 Drug interactions Table. Indiana University School of Medicine (2007). http://medicine.iupui.edu/clinpharm/ddis/table.aspx webcite. Accessed 13th May 2013
• [20]Lockhart DJ, Dong H, Byrne MC, et al.: Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat Biotechnol 1996, 14:1675-1680.
• [21]Ragoussis J, Elvidge G: Affymetrix GeneChip® system: moving from research to the clinic. Exp Rev Mol Diagnost 2006, 6:145-152.
• [22]Golub TR, Slonim DK, Tamayo P, et al.: Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999, 286:531-537.
• [23]St. Charles FK, Ashley M, Shepperd CJ, Clayton P, Errington GA: Robust method for estimating human smoked cigarette yields from filter analysis data. Beit Tabakforsch Int 2009, 23:232-243.
• [24]McEwan W: Breathe in, breathe out. Tob J Int 2010, 17:97.