Low Nicotine Content Cigarettes in Vulnerable Populations: Women of Reproductive Age

Despite marked reductions in cigarette smoking in the general population, smoking among economically disadvantaged women has increased. Smoking among women of reproductive age is a particular concern because in addition to the usual health risks, there are additional risks should they become pregnant. A national nicotine reduction policy for cigarettes has considerable potential to reduce tobacco use, dependence, and improve health in this population. Controlled trials in general population samples have demonstrated that reducing the nicotine content in cigarettes can reduce cigarettes per day (CPD), dependence severity, and tobacco toxicant exposure.

The goal of the proposed trial is to experimentally examine whether increasing the availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) enhances the effect of altering the nicotine in cigarettes in non-pregnant female cigarette smokers of childbearing age. Additionally, investigators will test whether allowing participants to personalize the flavor of the e-liquid alters any moderating effects their availability may have on tobacco cigarette smoking.

Daily smokers who are female, aged 21-44 years, and have a maximum educational attainment of graduating high school, will be recruited at Johns Hopkins University and the University of Vermont.

Investigators will study two research cigarettes referred to here as Research Cigarettes 1 (RC1) and Research Cigarettes 2 (RC2). One will be a normal nicotine content cigarette and the other a reduced nicotine content cigarette. Investigators will study two e-cigarette conditions referred to here as E-Cigarette Condition 1 (EC1) and E-Cigarette Condition 2 (EC2). Both e-cigarette conditions will involve the same commercially available devices and same nicotine-containing e-liquid, but in one condition that e-liquid will be available only in tobacco flavor while in the other the e-liquid will be available in multiple flavors from which participants can choose three based on personal preference. Participants will be assigned to one of the following four conditions: (1) RC1 only; (2) RC2 only; (3) RC2 + EC1; (4) RC2 + EC2.

Participants will be asked to use only their assigned study products for 16 weeks. Outcome measures include total CPD, craving, withdrawal, psychiatric symptoms, breath carbon monoxide (CO), other biomarkers of tobacco toxicant exposure, and cigarette demand assessed by behavioral economic purchase tasks.

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorder
• Intervention / Treatment: Other: Varying the nicotine content of cigarettes; Other: E-Cigarettes

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female
• 21 to 44 years old

Exclusion Criteria:

• Male
• Under 21 years old
• Over 44 years old

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC 2 only; Research Cigarettes #2	Other: Varying the nicotine content of cigarettes; 1) Altering the nicotine content of the tobacco research cigarettes; Other Names: Comparing normal nicotine content (RC1) to very low nicotine content (RC2)
Experimental: RC 2 + EC 1; Research Cigarettes #2 plus E-cigarettes #1	Other: Varying the nicotine content of cigarettes; 1) Altering the nicotine content of the tobacco research cigarettes; Other Names: Comparing normal nicotine content (RC1) to very low nicotine content (RC2); Other: E-Cigarettes; Comparing effects of combining RC2 with EC 1 versus EC2; Other Names: e-cigarette with only tobacco flavor (EC 1); e-cigarette in multiple flavors ( EC2)
Experimental: RC 2 + EC 2; Research Cigarettes #2 plus E-cigarettes #2	Other: Varying the nicotine content of cigarettes; 1) Altering the nicotine content of the tobacco research cigarettes; Other Names: Comparing normal nicotine content (RC1) to very low nicotine content (RC2); Other: E-Cigarettes; Comparing effects of combining RC2 with EC 1 versus EC2; Other Names: e-cigarette with only tobacco flavor (EC 1); e-cigarette in multiple flavors ( EC2)
Experimental: RC 1 only; Research cigarettes #1	Other: Varying the nicotine content of cigarettes; 1) Altering the nicotine content of the tobacco research cigarettes; Other Names: Comparing normal nicotine content (RC1) to very low nicotine content (RC2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Cigarettes Smoked Per Day	Cigarettes per day will be assessed for use of cigarettes with different nicotine content.	16 weeks

Collaborators and Investigators

• Sponsor: University of Vermont
• Collaborators: National Institute on Drug Abuse (NIDA); Johns Hopkins University; Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Stephen T. Higgins, Ph.D., University of Vermont

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2020
• Primary Completion (Actual): November 27, 2023
• Study Completion (Actual): November 27, 2023

Study Registration Dates

• First Submitted: September 13, 2019
• First Submitted That Met QC Criteria: September 13, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Women; Health Disparities; Nicotine Dependence; Biomarkers of Exposure; Reduced Nicotine Cigarettes; Tobacco Withdrawal; Vulnerable Populations; E-Cigarettes
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: CHRMS19-0129; U54DA036114-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: de-identified data
• IPD Sharing Time Frame: Data will be made available once we have published the results of the parent trials and manuscripts based on secondary analyses of those data, which we anticipate taking approximately three years
• IPD Sharing Access Criteria: request data for stated scientific purpose
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No