The Role of Nicotine and Non-Nicotine Alkaloids in E-Cigarette Use and Dependence

NCT02590393 | Completed Phase 1

• 2 other identifiers: Pro000597801R01DA038554-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The advent of electronic cigarette (e-cigarette) technologies represents one of the most significant developments in the last several decades, and provides a novel and promising strategy for substantially reducing the morbidity and mortality associated with smoking. However, serious concerns have been raised regarding the possibility that e-cigarettes will sustain a dependency on nicotine and that they may lead to continued use of conventional cigarettes known to be extremely harmful to health. Cigarette addiction critically involves a dependence on nicotine, but it is likely that other tobacco constituents contribute to dependence as well. Recent evidence suggests that non-nicotine tobacco alkaloids, or NNTAs (including anabasine, anatabine, nornicotine, and myosmine) may play a role in tobacco dependence. These alkaloids have been shown to augment the reinforcing effects of nicotine in animal models and to affect cravings in human smokers. E-cigarettes contain variable quantities of nicotine and NNTAs, but there is virtually no information available concerning the role of e-cigarette nicotine or NNTA content in influencing the concurrent use of cigarettes and e-cigarettes, when smokers attempt to switch from conventional combustible cigarettes to e-cigarettes. Additionally, it is not known whether the presence of nicotine and NNTAs in e- cigarettes may sustain dependence, making it difficult to relinquish these products. The proposed project will assess the acceptability, extent of switching behavior, and degree of dependence maintained when smokers are provided with e-cigarettes containing nicotine and NNTAs.

Conditions

Nicotine Dependence

Keywords

Nicotine addiction; Cigarette smoking; E-cigarettes

Outcome Measures

Primary Outcomes (1)

• Change in expired air carbon monoxide (CO) to assess recent smoking

  Self-reported changes in cigarette use from baseline to week 8, expressed as a percentage of baseline values, will be calculated, based on expired air carbon monoxide readings.

  Weeks 1-8

Secondary Outcomes (5)

• Mean volume of e-cigarette solution used per day to assess e-cigarette use.

  Weeks 1-8

• Change in cigarette use, assessed by self-report in daily dairies

  Weeks 1-8

• E-cigarette use, assessed by self-report in daily dairies

  Weeks 1-8

• Change in Nicotine dependence

  Weeks 1-8.

• Satisfaction ratings

  Weeks 1-8.

Study Arms (1)

Nicotine + NNTAs

EXPERIMENTAL

Participants will be asked to switch from cigarette use to use of e-cigarettes for eight weeks. E-cigarette cartridges will contain tobacco extract with nicotine + NNTAs in a vehicle of propylene glycol and vegtable glycerin, with tobacco or menthol flavor matched to each participant's preference. The yields of nicotine and NNTAs will be in the range of typical commercial cigarettes.

Combination Product: E-cigarettes

Interventions

E-cigarettes COMBINATION_PRODUCT

Participants will be asked to switch from cigarette use to use of e-cigarettes for eight weeks.

Also known as: Electronic Nicotine Delivery System (ENDS), e-cigs, electronic cigarettes

Nicotine + NNTAs

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have no known serious medical conditions;
• Are 21-65 years old;
• Smoke an average of at least 10 cigarettes per day;
• Have smoked at least one cumulative year;
• Have an expired air CO reading of at least 10ppm;
• Are able to read and understand English.
• Potential subjects must agree to use acceptable contraception during their participation in this study. Potential subjects must agree to avoid the following during their participation in this study:
• Participation in any other nicotine-related modification strategy outside of this protocol;
• Use of tobacco products other than cigarettes, including pipe tobacco, cigars, snuff, and chewing tobacco;
• Use of e-cigarettes other than the ones provided during the study;
• Use of experimental (investigational) drugs or devices;
• Use of illegal drugs.

You may not qualify if:

• Actively seeking treatment for nicotine dependence;
• Uncontrolled high blood pressure (self-report);
• Coronary heart disease with symptoms (e.g., chest pain);
• Heart attack in the past year;
• Cardiac rhythm disorder (irregular heart rhythm with symptoms);
• Chest pain in the last month (unless history indicates a non-cardiac source);
• Symptomatic heart disorder such as heart failure;
• Advanced liver or kidney disease that requires medication or dialysis, paracentesis;
• Bleeding stomach ulcers in the past 30 days;
• Lung disease that requires oxygen;
• Major brain disorder (including stroke with residual deficit, brain tumor, and seizure disorder);
• Migraine headaches that occur more frequently than once per week;
• Recent, unexplained fainting spells;
• Diabetes with insulin use;
• Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);

Sponsors & Collaborators

• Duke University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Duke Center for Smoking Cessation

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Cigarette Smoking; Vaping

Interventions

Electronic Nicotine Delivery Systems

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Jed Rose, Ph.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: October 29, 2015
• Study Start: May 21, 2021
• Primary Completion: January 13, 2022
• Study Completion: January 13, 2022
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)