Low Nicotine Content Cigarettes in Vulnerable Populations: Affective Disorders

NCT04090879 | Completed Phase 2 Results DMC

• 2 other identifiers: CHRMS19-0129U54DA036114-06
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 2

Brief Summary

While the prevalence of smoking in the United States general population has declined over the past 50 years, there has been little to no decline among people with mental health conditions. Affective Disorders (ADs) are the most common mental health conditions in the US, and over 40% of people with ADs are current smokers. A national policy of reducing the nicotine content of cigarettes has the potential to reduce tobacco use, dependence, and related adverse health outcomes. Controlled trials in psychiatrically-stable smokers have shown that reducing the nicotine content in cigarettes can reduce cigarettes per day (CPD), dependence and tobacco toxicant exposure, with few adverse consequences. The goal of the proposed trial is to experimentally model whether increasing the availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) moderates the effect of altering the nicotine in cigarettes in smokers with ADs. 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 with current ADs will be recruited at Brown University and the University of Vermont. Investigators will study two research cigarettes referred to here as Research Cigarette 1 (RC1) and Research Cigarette 2 (RC2). One of these cigarettes will be a normal nicotine content cigarette and the other will be 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 condition that e-liquid will be available in multiple flavors from which participants can choose based on personal taste preference. Participants will be assigned to one of the following four study 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, cigarette demand assessed by behavioral economics-based purchase tasks, craving, withdrawal, psychiatric symptoms, breath carbon monoxide (CO), biomarkers of tobacco toxicant exposure, brain function and structure, and airway inflammation (fractional nitric oxide concentration in exhaled breath \[FeNO\]).

Conditions

Tobacco Use Disorder

Keywords

Biomarkers of Exposure; Compensatory Smoking; Nicotine Dependence; Reduced Nicotine Cigarettes; Affective Disorders; Tobacco Withdrawal; Vulnerable Populations; E-Cigarettes

Outcome Measures

Primary Outcomes (1)

• Cigarettes Per Day

  Cigarettes per day will be assessed for use of cigarettes with different nicotine content.

  16 weeks

Study Arms (4)

RC 1 only

EXPERIMENTAL

Research Cigarettes #1

Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

RC 2 only

EXPERIMENTAL

Research Cigarettes #2

Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)

RC 2 + EC 1

EXPERIMENTAL

Research Cigarettes #2 plus E-cigarettes #1 (participants receive tobacco flavor only)

Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g); Other: E-Cigarettes

RC 2 + EC 2

EXPERIMENTAL

Research Cigarettes #2 plus E-cigarettes #2 (participants can choose among varying flavors)

Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g); Other: E-Cigarettes

Interventions

Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g) OTHER

1\) Altering the nicotine content of the tobacco research cigarette

RC 1 only; RC 2 + EC 1; RC 2 + EC 2; RC 2 only

E-Cigarettes OTHER

1\) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition

RC 2 + EC 1; RC 2 + EC 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 21 years and 70 years old
• Must have current diagnosis of an Affective Disorder.

You may not qualify if:

• Being without an Affective Disorder
• Younger than 21 years old
• Older than 70 years old

Sponsors & Collaborators

• Brown University: lead
• Food and Drug Administration (FDA): collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• University of Vermont: collaborator

Study Sites (2)

Brown University

Providence, Rhode Island, 02912, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Related Publications (1)

• Higgins ST, Sigmon SC, Tidey JW, Heil SH, Gaalema DE, Lee DC, DeSarno MJ, Klemperer EM, Menson KE, Cioe PA, Plucinski S, Wiley RC, Orr E. Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials. JAMA Netw Open. 2024 Sep 3;7(9):e2431731. doi: 10.1001/jamanetworkopen.2024.31731.

  PMID: 39240566 DERIVED

MeSH Terms

Conditions

Tobacco Use Disorder; Mood Disorders; Vaping

Interventions

Electronic Nicotine Delivery Systems

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Jennifer W. Tidey
• Organization: Brown University

jennifer_tidey@brown.edu

4018636418

Study Officials

• Jennifer W Tidey, Ph.D.

  Brown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind dosing of tobacco cigarette nicotine levels.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized parallel groups research design

Study Record Dates

• First Submitted: September 13, 2019
• First Posted: September 16, 2019
• Study Start: October 18, 2020
• Primary Completion: November 27, 2023
• Study Completion: November 27, 2023
• Last Updated: April 1, 2025
• Results First Posted: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (2)