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

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

Changes in levels of biomarkers of exposure and biological effect in a controlled study of smokers switched from conventional cigarettes to reduced-toxicant-prototype cigarettes

AbstractBackgroundDevelopment of cigarettes that reduce exposure to harmful smoke constituents is a suggested tobacco harm reduction strategy, but robust methods for measurement of change are required. We investigated whether changes in biomarkers of exposure (BoE), effective dose (BoED) and biological effect (BoBE) could be detected after switching from conventional cigarettes to a reduced-toxicant-prototype cigarette (RTP).MethodsRegular smokers of 6–8mg ISO tar yield cigarettes were recruited in Hamburg, Germany, and supplied with a conventional 7mg ISO tar yield cigarette for 2weeks then switched to the same cigarette with a different tipping paper (control) or the RTP for 6months. Subjects smoked mostly at home and attended five residential clinic visits where urine and blood samples were collected for analysis. Primary endpoints were changes in specific biomarker levels compared with non-smoker background levels. Changes in daily cigarette consumption were also investigated.ResultsBoE levels in controls generally increased over the study period, whereas most BoE and all BoED significantly declined in RTP smokers. Most BoBE data were similar across groups and/or too variable within individuals to detect changes. Increased daily cigarette consumption was affected by supply of free cigarettes, perceived shorter smoking time per cigarette than usual brands, and perceived reduced harm.ConclusionsDespite increased cigarette consumption, reductions in BoE and BoED were detectable