Project 1, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Childbearing Age Women
Condition: Tobacco Use Disorder
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study will examine extended exposure to cigarettes varying in nicotine content among
      disadvantaged women. Disadvantaged women are at increased risk for smoking, nicotine
      dependence, and using high nicotine yield cigarettes and are also at significantly increased
      risk for smoking-related adverse health consequences, including cervical cancer, thrombosis
      related to hormone-based contraception, infertility, and early menopause. Studies testing an
      innovative regulatory strategy of reducing the nicotine content of cigarettes to a
      non-addictive level have shown promising beneficial effects (decreased smoking rate, reduced
      toxicant exposure, and increased cessation) in the general population of smokers. However,
      these studies have uniformly excluded vulnerable populations like disadvantaged women who may
      respond differently considering their greater vulnerability to smoking and nicotine
      dependence. Thus, little is known scientifically about how this highly vulnerable subgroup of
      smokers might respond to a nicotine reduction policy. This project is designed to address
      that substantial knowledge gap. This same study was also conducted in two additional
      vulnerable populations under a similar protocol.
    

Detailed description: 
      The primary overall objective of these studies is to evaluate the effects of extended
      exposure to cigarettes differing in nicotine content in socioeconomically disadvantaged (<
      high school educational attainment) women of childbearing age using a 3-condition, parallel
      groups design. After a baseline period in which daily smoking rate and other baseline
      assessments are completed, participants will be randomly assigned to one of three cigarette
      conditions (nicotine content: 0.04, 2.4, and 15.8 mg nicotine/gram of tobacco) for the
      12-week experimental period.

      The cigarettes to be used in this study were made under an NIH contract with production being
      overseen by the Research Triangle Institute (referred to as "Spectrum cigarettes"). NIH
      currently has approximately 10 million of these cigarettes (of varying types) for research
      purposes. The cigarettes selected for the study span the range of yields likely to produce
      the hypothesized effects, as described above. The Spectrum cigarettes are not currently
      commercially available, although they are similar in many ways to marketed cigarettes (e.g.,
      similar manufacturing, filter, paper, etc.).

      The primary overall objective of this study is to evaluate the effects of extended exposure
      to cigarettes differing in nicotine content in female adult smokers of childbearing age
      (18-44 yrs) whose highest academic degree is high school using a 3-condition, parallel groups
      design. After a baseline period in which daily smoking rate and other baseline assessments
      are completed, participants will be randomly assigned to one of three cigarette conditions
      (nicotine content: 0.04 mg, 2.4 mg, and 15.8 mg nicotine/g of tobacco) for the 12-week
      experimental period.

      Participants will be seen weekly throughout the 12-week experimental period to obtain
      research cigarettes. Cigarettes smoked per day will be obtained by participants completing
      daily Interactive Voice Response (IVR) reports of cigarettes in past 24 hours. This daily
      data will be used to calculate weekly means, with week-12 means serving as the primary
      outcome.

      This same study was conducted in two additional vulnerable populations under a similar
      protocol, with differences between protocols consisting of data collection specific to that
      vulnerable population. This included information such as use and timing of opioid maintenance
      therapy for individuals with opioid-use disorder or additional assessments of anxiety and
      depression for individuals with affective disorders. In order to explore potential
      differences across individuals with different vulnerabilities, data from all three studies
      were combined for analysis. A vulnerable population-by-condition or
      population-by-condition-by-time interaction term was included in all analyses. In the event
      that these interaction terms were statistically significant, all pairwise comparisons were
      conducted using a Bonferroni multiple comparison adjustment.
    

Intervention name(s): Very low nicotine content cigarettes
Intervention type(s): Other
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study was one of three multi-site clinical trials conducted in three different vulnerable populations under a similar protocol, with differences between protocols consisting of data collection specific to that vulnerable population. This included information such as use and timing of opioid maintenance therapy for individuals with opioid-use disorder or additional assessments of anxiety and depression for individuals with affective disorders. In order to explore potential differences across individuals with different vulnerabilities, data from all three studies were combined for analysis. A vulnerable population-by-condition or population-by- condition-by-time interaction term was included in all analyses. In the event that these interaction terms were statistically significant, all pairwise comparisons were conducted using a Bonferroni multiple comparison adjustment. Please see Statistical Analysis Plan for more details.
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Biomarkers of exposure; Compensatory smoking; Nicotine dependence; Reduced nicotine cigarettes; Tobacco withdrawal; Women; Health disparities; Vulnerable populations