Brief Summary

Three hundred-twenty (320) adult smokers of menthol or non-menthol combustible cigarettes will be recruited and randomly assigned to one of five groups (n=64/group), who will be asked to switch for 12 weeks to ad libitum use of combustible cigarettes (matched to subjects' menthol preference) containing either 0.4, 1.4, 2.5, 5.6 or 16.9 mg nicotine (standardized nicotine yields ranging from 0.02-0.80 mg/cigarette), respectively. Each group will include 32 heavy (≥ 20 cigarettes/day), and 32 light smokers (≤10 cigarettes/day), who are hypothesized to be more sensitive to nicotine's reinforcing effects. Participants will also have free access to nicotine-containing e-cigarettes (JUUL) throughout the 12-week period. Abuse liability of combustible cigarettes will be assessed by behavioral (cigarettes/day, time to first cigarettes), self-report (rewarding effects, withdrawal symptoms) and biochemical indices (expired air carbon monoxide, cotinine blood sampling). In laboratory sessions, we will measure nicotine thresholds for detecting and recognizing the addictive, rewarding effects of smoking. This study is designed to help the FDA identify a target nicotine threshold that will not attract young people to smoking or induce relapse in former smokers. Additionally, we will determine the level of cigarette nicotine reduction that will be tolerated without inducing dissatisfaction in smokers, information that is relevant to the FDA for designing a stepwise nicotine reduction policy that can be implemented without widespread objections. The knowledge gained from this project will greatly increase our knowledge of nicotine addiction and will help frame an FDA policy relating to the regulation of the nicotine content of tobacco. Ultimately, a well-designed nicotine reduction policy has the potential to greatly reduce the enormous toll of death and disease caused by cigarette smoking.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

150

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started May 2019

Geographic Reach

1 country

2 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

2.2 years study duration

First Submitted

Initial submission to the registry

August 10, 2016

Completed

7 days until next milestone

First Posted

Study publicly available on registry

August 17, 2016

Completed

2.7 years until next milestone

Study Start

First participant enrolled

May 1, 2019

Completed

2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 28, 2021

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 28, 2021

Completed

Last Updated

January 14, 2022

Status Verified

January 1, 2022

Enrollment Period

2.2 years

First QC Date

August 10, 2016

Last Update Submit

January 12, 2022

Conditions

Nicotine Addiction Cigarette Smoking

Outcome Measures

Primary Outcomes (1)

Expired air CO Measurement
To determine the effects of cigarette nicotine content manipulations on abuse liability as measured by exhaled breath CO.
12 Weeks

Secondary Outcomes (5)

Nicotine discrimination tests to determine nicotine detection thresholds
Weeks 1, 2,8,10,12 and 14
Nicotine discrimination tests to determine nicotine recognition thresholds
Weeks 1, 2,8,10,12 and 14
Extent of e-cigarette use based on self-report
12 Weeks
Extent of e-cigarette use based on self-report cotinine levels
12 Weeks
Mean number of research cigarettes smoked per day as primary index of abuse liability
12 Weeks

Study Arms (7)

0.40mg Nicotine Cigarette w/ e-Cigarette

ACTIVE COMPARATOR

Participants will be assigned to smoke 0.40mg nicotine Spectrum cigarettes for 12 weeks with unlimited access to JUUL e-cigarettes. Smoking research cigarettes with e-cigarette