Clinical trial NCT02250534: Project 1, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Childbearing Age Women
Official title: Project 1, Study 2: Extended Exposure to Low Nicotine Content Cigarettes in Childbearing Age Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tobacco Use Disorder
Keywords: Biomarkers of exposure
Compensatory smoking
Nicotine dependence
Reduced nicotine cigarettes
Tobacco withdrawal
Women
Health disparities
Vulnerable populations
Lead sponsor: University of Vermont
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: National Institute on Drug Abuse (NIDA)
First posted: 2014-09-26
Enrollment: 775
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Female
* Ages 18-44 years
* Less than an Associate's degree
* Report smoking ≥ 5 cigarettes per day
* Provide an intake breath carbon monoxide (CO) sample \> 8 ppm
* Be without current (within the past year) serious mental disorder that would interfere with study results or completion as determined by the Licensed Medical Professional or PI
* Be without current substance abuse/dependence other than nicotine
* Be sufficiently literate to complete research-related tasks
* Be in good physical health without serious illness or change in health or medication in the past three months as determined by the Licensed Medical Professional at each site
* Not pregnant or nursing and report using oral, implant, patch, ring, intrauterine device (IUD), injection, or barrier contraceptives or report being surgically sterile, or post menopausal
* Report no significant use of other tobacco or nicotine products within the past month (\> 9 days in the past 30)

Exclusion Criteria:

* Any prior regular use (used as primary cigarette outside of the laboratory) of Spectrum cigarettes (i.e., research cigarettes with reduced nicotine content)
* Exclusive use of roll-your-own cigarettes
* Planning to quit smoking in the next 30 days
* A quit attempt in the past 30 days resulting in \> 3 days of abstinence
* Currently taking anticonvulsant medications
* Positive toxicology screen for illicit drugs not including marijuana (participants with valid prescriptions will not be excluded and participants with a positive toxicology screen will be allowed to re-screen once)
* Breath alcohol level \> 0.01 (participants with a positive screen will be allowed to re-screen once)
* Self-report of binge drinking alcohol (\> 9 days in past 30, 4 drinks in 2 hours )
* Systolic blood pressure \< 90 or ≥ 160 mmHg (participants outside the range will be allowed to re-screen once)
* Diastolic blood pressure \< 50 or ≥ 100 mmHg (participants outside the range will be allowed to re-screen once)
* Breath CO \> 80 ppm
* Heart rate \< 45 or ≥ 115 bpm (participants outside the range will be allowed to re-screen once)
* Currently seeking treatment for smoking cessation
* Have used nicotine replacement, bupropion or other pharmacotherapies as cessation aids in the past month (bupropion for treatment of depression will be allowed)
* Current symptoms of psychosis, dementia or mania
* Suicidal ideation in the past month
* Suicide attempt in past 6 months
* Participation in another research study in the past 30 days

Primary outcomes:
measure: Cigarettes Per Day (CPD)
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
Study officials:
affiliation: University of Vermont
name: Stephen T. Higgins, Ph.D.
role: STUDY_DIRECTOR
affiliation: University of Vermont
name: Sarah H. Heil, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaalema DE, Snell LM, Tidey JW, Sigmon SC, Heil SH, Lee DC, Bunn JY, Park C, Hughes JR, Higgins ST. Potential effects of nicotine content in cigarettes on use of other substances. Prev Med. 2022 Dec;165(Pt B):107290. doi: 10.1016/j.ypmed.2022.107290. Epub 2022 Oct 5.
citation: Oliver AC, DeSarno M, Irvin CG, Kaminsky D, Tidey JW, Sigmon SC, Heil SH, Gaalema DE, Lee D, Bunn JY, Davis DR, Streck JM, Gallagher T, Higgins ST. Effects of Reduced Nicotine Content Cigarettes on Fractional Exhaled Nitric Oxide and Self-Reported Respiratory Health Outcomes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage. Nicotine Tob Res. 2022 Jan 1;24(1):135-140. doi: 10.1093/ntr/ntab145.
citation: Higgins ST, DeSarno M, Bunn JY, Gaalema DE, Leventhal AM, Davis DR, Streck JM, Harfmann RF, Markesich C, Orr E, Sigmon SC, Heil SH, Tidey JW, Lee D, Hughes JR. Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes. Prev Med. 2021 Nov;152(Pt 2):106714. doi: 10.1016/j.ypmed.2021.106714. Epub 2021 Jul 7.
citation: Higgins ST, Tidey JW, Sigmon SC, Heil SH, Gaalema DE, Lee D, Hughes JR, Villanti AC, Bunn JY, Davis DR, Bergeria CL, Streck JM, Parker MA, Miller ME, DeSarno M, Priest JS, Cioe P, MacLeod D, Barrows A, Markesich C, Harfmann RF. Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials. JAMA Netw Open. 2020 Oct 1;3(10):e2019311. doi: 10.1001/jamanetworkopen.2020.19311.
citation: Higgins ST, DeSarno M, Davis DR, Nighbor T, Streck JM, Adise S, Harfmann R, Nesheim-Case R, Markesich C, Reed D, Tyndale RF, Gaalema DE, Heil SH, Sigmon SC, Tidey JW, Villanti AC, Lee D, Hughes JR, Bunn JY. Relating individual differences in nicotine dependence severity to underpinning motivational and pharmacological processes among smokers from vulnerable populations. Prev Med. 2020 Nov;140:106189. doi: 10.1016/j.ypmed.2020.106189. Epub 2020 Jul 3.