Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure a randomized clinical trial

Dorothy K Hatsukami, Xianghua Luo, Joni A. Jensen, Mustafa N al'Absi, Sharon S Allen, Steven G Carmella, Menglan Chen, Paul M. Cinciripini, Rachel Denlinger-Apte, David J. Drobes, Joe Koopmeiners, Tonya Lane, Chap T Le, Scott Leischow, Kai Luo, F. Joseph McClernon, Sharon E Murphy, Viviana Paiano, Jason D. Robinson, Herbert Severson & 8 others Christopher Sipe, Andrew A. Strasser, Lori S Strayer, Mei Kuen Tang, Ryan Vandrey, Stephen S Hecht, Neal L. Benowitz, Eric C. Donny

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

IMPORTANCE: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. OBJECTIVES: To 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 PARTICIPANTS: A 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 MEASURES: Between-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. RESULTS: Among 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 RELEVANCE: Among 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.

Original languageEnglish (US)
Pages (from-to)880-891
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume320
Issue number9
DOIs
StatePublished - Sep 4 2018

Fingerprint

hydroxypropyl methacrylate
Nicotine
Smoke
Tobacco Products
Randomized Controlled Trials
Biomarkers
Carbon Monoxide
Tobacco
Control Groups
Urine
Acrolein
Polycyclic Aromatic Hydrocarbons
Volunteers
Smoking
Maintenance

PubMed: MeSH publication types

  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

Cite this

Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure a randomized clinical trial. / Hatsukami, Dorothy K; Luo, Xianghua; Jensen, Joni A.; al'Absi, Mustafa N; Allen, Sharon S; Carmella, Steven G; Chen, Menglan; Cinciripini, Paul M.; Denlinger-Apte, Rachel; Drobes, David J.; Koopmeiners, Joe; Lane, Tonya; Le, Chap T; Leischow, Scott; Luo, Kai; Joseph McClernon, F.; Murphy, Sharon E; Paiano, Viviana; Robinson, Jason D.; Severson, Herbert; Sipe, Christopher; Strasser, Andrew A.; Strayer, Lori S; Tang, Mei Kuen; Vandrey, Ryan; Hecht, Stephen S; Benowitz, Neal L.; Donny, Eric C.

In: JAMA - Journal of the American Medical Association, Vol. 320, No. 9, 04.09.2018, p. 880-891.

Research output: Contribution to journalArticle

Hatsukami, DK, Luo, X, Jensen, JA, al'Absi, MN, Allen, SS, Carmella, SG, Chen, M, Cinciripini, PM, Denlinger-Apte, R, Drobes, DJ, Koopmeiners, J, Lane, T, Le, CT, Leischow, S, Luo, K, Joseph McClernon, F, Murphy, SE, Paiano, V, Robinson, JD, Severson, H, Sipe, C, Strasser, AA, Strayer, LS, Tang, MK, Vandrey, R, Hecht, SS, Benowitz, NL & Donny, EC 2018, 'Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure a randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 320, no. 9, pp. 880-891. https://doi.org/10.1001/jama.2018.11473
Hatsukami, Dorothy K ; Luo, Xianghua ; Jensen, Joni A. ; al'Absi, Mustafa N ; Allen, Sharon S ; Carmella, Steven G ; Chen, Menglan ; Cinciripini, Paul M. ; Denlinger-Apte, Rachel ; Drobes, David J. ; Koopmeiners, Joe ; Lane, Tonya ; Le, Chap T ; Leischow, Scott ; Luo, Kai ; Joseph McClernon, F. ; Murphy, Sharon E ; Paiano, Viviana ; Robinson, Jason D. ; Severson, Herbert ; Sipe, Christopher ; Strasser, Andrew A. ; Strayer, Lori S ; Tang, Mei Kuen ; Vandrey, Ryan ; Hecht, Stephen S ; Benowitz, Neal L. ; Donny, Eric C. / Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure a randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2018 ; Vol. 320, No. 9. pp. 880-891.
@article{b38851d5c278456ca79ef386bf08a3fb,
title = "Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure a randomized clinical trial",
abstract = "IMPORTANCE: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. OBJECTIVES: To 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 PARTICIPANTS: A 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 MEASURES: Between-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. RESULTS: Among 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 RELEVANCE: Among 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.",
author = "Hatsukami, {Dorothy K} and Xianghua Luo and Jensen, {Joni A.} and al'Absi, {Mustafa N} and Allen, {Sharon S} and Carmella, {Steven G} and Menglan Chen and Cinciripini, {Paul M.} and Rachel Denlinger-Apte and Drobes, {David J.} and Joe Koopmeiners and Tonya Lane and Le, {Chap T} and Scott Leischow and Kai Luo and {Joseph McClernon}, F. and Murphy, {Sharon E} and Viviana Paiano and Robinson, {Jason D.} and Herbert Severson and Christopher Sipe and Strasser, {Andrew A.} and Strayer, {Lori S} and Tang, {Mei Kuen} and Ryan Vandrey and Hecht, {Stephen S} and Benowitz, {Neal L.} and Donny, {Eric C.}",
year = "2018",
month = "9",
day = "4",
doi = "10.1001/jama.2018.11473",
language = "English (US)",
volume = "320",
pages = "880--891",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "9",

}

TY - JOUR

T1 - Effect of immediate vs gradual reduction in nicotine content of cigarettes on biomarkers of smoke exposure a randomized clinical trial

AU - Hatsukami, Dorothy K

AU - Luo, Xianghua

AU - Jensen, Joni A.

AU - al'Absi, Mustafa N

AU - Allen, Sharon S

AU - Carmella, Steven G

AU - Chen, Menglan

AU - Cinciripini, Paul M.

AU - Denlinger-Apte, Rachel

AU - Drobes, David J.

AU - Koopmeiners, Joe

AU - Lane, Tonya

AU - Le, Chap T

AU - Leischow, Scott

AU - Luo, Kai

AU - Joseph McClernon, F.

AU - Murphy, Sharon E

AU - Paiano, Viviana

AU - Robinson, Jason D.

AU - Severson, Herbert

AU - Sipe, Christopher

AU - Strasser, Andrew A.

AU - Strayer, Lori S

AU - Tang, Mei Kuen

AU - Vandrey, Ryan

AU - Hecht, Stephen S

AU - Benowitz, Neal L.

AU - Donny, Eric C.

PY - 2018/9/4

Y1 - 2018/9/4

N2 - IMPORTANCE: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. OBJECTIVES: To 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 PARTICIPANTS: A 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 MEASURES: Between-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. RESULTS: Among 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 RELEVANCE: Among 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.

AB - IMPORTANCE: The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. OBJECTIVES: To 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 PARTICIPANTS: A 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 MEASURES: Between-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. RESULTS: Among 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 RELEVANCE: Among 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.

UR - http://www.scopus.com/inward/record.url?scp=85053007235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053007235&partnerID=8YFLogxK

U2 - 10.1001/jama.2018.11473

DO - 10.1001/jama.2018.11473

M3 - Article

VL - 320

SP - 880

EP - 891

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 9

ER -