Dataset Information

Effects of immediate versus gradual nicotine reduction in cigarettes on biomarkers of biological effects.

ABSTRACT: AIM:A previous study showed significantly greater reductions in number of cigarettes smoked and biomarkers of toxicant and carcinogen exposure in smokers assigned to immediate reduction of nicotine in cigarettes to very low levels versus gradually over time or continued smoking of normal nicotine content cigarettes. This study examines the effects of these approaches on selected biomarkers associated with harmful biological effects. DESIGN:Three-arm, randomized controlled trial. SETTING:Ten United States academic institutional sites. PARTICIPANTS:Daily smokers uninterested in quitting smoking with a mean age of 45.1 [standard deviation (SD) = 13.4)] years and smoking 17.1 (SD = 8.5) cigarettes/day; 43.9% (549 of 1250) female; 60.6% (758 of 1250) white ethnicity. INTERVENTIONS:(1) Smoking cigarettes where nicotine content was immediately reduced to very low levels (n = 503); (2) smoking cigarettes where nicotine content was gradually reduced, with dose changes occurring monthly (n = 498); and (3) continued smoking with normal nicotine content cigarettes (n = 249). MEASUREMENTS:Smokers were assessed at baseline while smoking their usual brand cigarettes, and again at 4, 8, 12, 16 and 20 weeks. Outcomes were areas under the concentration time curve (AUC) for the period of study of biomarkers of inflammation, oxidative stress and hematological parameters. FINDINGS:No consistent significant differences were observed across groups (Bayes factors showing data to be insensitive), with the only exception being red blood cell size variability, which was observed to be lower in the immediate versus gradual nicotine reduction [mean difference = -0.11; 95% confidence interval (CI) = -0.18, -0.04, P = 0.004] and normal nicotine control groups (mean difference = - 0.15, 95% CI = -0.23, -0.06, P = 0.001). CONCLUSION:It remains unclear whether switching to very low nicotine cigarettes leads to a short-term reduction in biomarkers of tobacco-related harm.

SUBMITTER: Hatsukami DK

PROVIDER: S-EPMC6732016 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of immediate versus gradual nicotine reduction in cigarettes on biomarkers of biological effects.

Hatsukami Dorothy K DK Luo Xianghua X Heskin Alisa K AK Tang Mei Kuen MK Carmella Steven G SG Jensen Joni J Robinson Jason D JD Vandrey Ryan R Drobes David J DJ Strasser Andrew A AA al'Absi Mustafa M Leischow Scott S Cinciripini Paul M PM Koopmeiners Joseph J Ikuemonisan Joshua J Benowitz Neal L NL Donny Eric C EC Hecht Stephen S SS

Addiction (Abingdon, England) 20190708 10

<h4>Aim</h4>A previous study showed significantly greater reductions in number of cigarettes smoked and biomarkers of toxicant and carcinogen exposure in smokers assigned to immediate reduction of nicotine in cigarettes to very low levels versus gradually over time or continued smoking of normal nicotine content cigarettes. This study examines the effects of these approaches on selected biomarkers associated with harmful biological effects.<h4>Design</h4>Three-arm, randomized controlled trial.<h ...[more]

PMID: 31140663

Similar Datasets

Project description:ImportanceThe optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined.ObjectivesTo determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure.Design, setting, and participantsA double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017.Interventions(1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes.Main outcomes and measuresBetween-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention.ResultsAmong 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, -4.06 parts per million [ppm] [95% CI, -4.89 to -3.23]; P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93]; P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, -3.38 [95% CI, -4.40 to -2.36]; P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88]; P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92]; P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, -0.31 to 1.67]; P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06]; P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04]; P = .52).Conclusions and relevanceAmong smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control.Trial registrationclinicaltrials.gov Identifier: NCT02139930.

Project description:BackgroundA recent clinical trial showed that an immediate transition to very low nicotine content (VLNC) cigarettes, compared with a gradual transition, produced greater reductions in smoking behavior, smoke exposure, and dependence. However, there was less compliance with the instruction to smoke only VLNC cigarettes in the immediate versus gradual reduction condition. The goal of this study was to test whether nicotine reduction method alters subjective ratings of VLNC cigarettes, and whether subjective ratings mediate effects of nicotine reduction method on smoking behavior, smoke exposure, dependence, and compliance.MethodsThis is a secondary analysis of a randomized trial conducted across 10 sites in the United States. Smokers (n = 1250) were randomized to either a control condition, or to have the nicotine content of their cigarettes reduced immediately or gradually to 0.04 mg nicotine/g of tobacco during a 20-week study period. Participants completed the modified Cigarette Evaluation Questionnaire (mCEQ).ResultsAfter Week 20, the immediate reduction group scored significantly lower than the gradual reduction group on multiple subscales of the mCEQ (ps < .001). The Satisfaction subscale of the mCEQ mediated the impact of nicotine reduction method on smoke exposure, smoking behavior, dependence, compliance, and abstinence. Other subscales also mediated a subset of these outcomes.ConclusionsAn immediate reduction in nicotine content resulted in lower product satisfaction than a gradual reduction, suggesting that immediate reduction further reduces cigarette reward value. This study will provide the Food and Drug Administration with information about the impact of nicotine reduction method on cigarette reward value.ImplicationsThese data suggest that an immediate reduction in nicotine content will result in greater reductions in cigarette satisfaction than a gradual reduction, and this reduction in satisfaction is related to changes in smoking behavior and dependence.

Project description:Electronic cigarette (EC) use is growing dramatically with use highest among young adults and current smokers. One of the most common reasons for using ECs is interest in quitting or reducing cigarettes per day (CPD); however there are few randomized controlled trials (RCT) on the effect of ECs on smoking abstinence and reduction.We conducted a two-arm; double-blind RCT. Subjects were randomized to receive 3-weeks of either disposable 4.5% nicotine EC (intervention) or placebo EC. The primary outcome was self-reported reduction of at least 50% in the number of CPDs smoked at week 3 (end of treatment) compared to baseline. Study subjects (n = 99) were young adult (21-35), current smokers (smoked ? 10 CPDs) living in NYC.Compared with baseline, a significant reduction in CPDs was observed at both study time periods (1 and 3 weeks) for intervention (P < .001) and placebo (P < .001) groups. Between-group analyses showed significantly fewer CPDs in the intervention group compared to the placebo group at week 3 (P = .03), but not at any other follow-up periods. The logistic regression analysis showed that using a greater number of ECs, treatment condition and higher baseline readiness to quit were significantly associated with achieving at least 50% reduction in CPDs at the end of treatment.A diverse young adult sample of current everyday smokers, who were not ready to quit, was able to reduce smoking with the help of ECs. Further study is needed to establish the role of both placebo and nicotine containing ECs in increasing both reduction and subsequent cessation.Despite the critical need for well-designed clinical trials on the effect of ECs on cessation and cigarette reduction, the majority of studies have been observational or noncomparative intervention designs. Only three RCTs studying ECs as a cessation or reduction intervention have been published, and none were conducted in the United States. The current study adds knowledge to current literature on the feasibility of using ECs to aid smoking reduction among young smokers in US urban populations.

Project description:IntroductionDual use of electronic cigarettes (e-cigarettes) and combustible cigarettes is a major public health issue. It is generally accepted that exclusive e-cigarette use is less harmful than exclusive combustible cigarette use, but most e-cigarette users continue to smoke combustible cigarettes as well. To what extent the use of e-cigarettes reduces harm in people who continue to smoke combustible cigarettes has been debated. The aim of this study was to explore the utility of biomarkers as measures of dual use.MethodsIn two human studies of participants who used e-cigarettes only or both combustible cigarettes and e-cigarettes, we measured urine concentrations of the metabolites of nicotine (total nicotine equivalents) as well as two biomarkers of tobacco exposure: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen metabolite, and nicotelline, a tobacco alkaloid not found in significant concentrations in e-cigarette products.ResultsThe presence of nicotine metabolites indicates either e-cigarette or combustible cigarette use. Nicotelline (half-life of 2-3 hours) indicates recent combustible cigarette use and NNAL (half-life of 10 days or more), indicates combustible cigarette use occurring within several weeks prior to sample collection.ConclusionsNicotelline and NNAL are useful biomarkers for combustible tobacco use in users e-cigarettes. The application of these biomarkers provides a tool to help assess whether, or to what extent, dual use of e-cigarettes and combustible cigarettes reduces harm compared to sole use of combustible cigarettes. These biomarkers can also verify exclusive use of e-cigarettes over short (24 hour) or long (several week) time periods.ImplicationsTo what extent dual use of e-cigarettes and combustible cigarettes reduce harm compared to smoking combustible cigarettes only is of considerable public health interest. We show that the levels of the minor tobacco alkaloid nicotelline and the nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are extremely low in electronic cigarette fluids. The urine biomarkers nicotelline and the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are indicative of cigarette smoking and can be used to assess recent and past smoking in dual users.

Project description:IntroductionBecause 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy.MethodsIn a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence.ResultsAt baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (-6.4 vs. -9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (-4.5 vs. -7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition.ConclusionsAlthough menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers.ImplicationsResults of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes.

Dataset Information

Effects of immediate versus gradual nicotine reduction in cigarettes on biomarkers of biological effects.

Publications

Effects of immediate versus gradual nicotine reduction in cigarettes on biomarkers of biological effects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets