Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder

NCT04092101 | Completed Phase 2 Results DMC

• 2 other identifiers: CHRMS19-0130U54DA036114-06
• Study Type: interventional
• Target: 326
• Locations: 1 country
• Sites: 2

Brief Summary

Prevalence of smoking among individuals with opioid use disorder (OUD) is six-fold that of the general US adult population. The mortality rate of opioid-dependent smokers is four times that of opioid-dependent nonsmokers, and their response to smoking cessation interventions is notoriously poor. A national policy of reducing the nicotine content of cigarettes has the potential to be an effective method of reducing tobacco use prevalence, dependence, and related adverse health outcomes. Controlled trials in the general smoker population have demonstrated that switching smokers to low nicotine content cigarettes results in reductions in cigarettes per day (CPD), dependence and tobacco toxicant exposure, with few adverse consequences. The investigators believe that the impact of reduced nicotine standards on use of combusted cigarettes in this population will be moderated considerably by other tobacco market conditions including (1) availability of alternative sources of non-combusted nicotine, and (2) whether these alternatives are available under conditions that optimize their appeal. The investigators hypothesize the same for other vulnerable populations as well, but achieving significant reductions in use of combusted cigarettes in smokers with OUD seems especially unlikely in the absence of readily available and appealing alternative sources of non-combusted nicotine. The goal of the proposed trial is to experimentally model whether increased availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) will enhance the effectiveness of a reduced nicotine standard for cigarettes in smokers with OUD. Additionally, the investigators will test whether allowing participants to personalize the favor of the e-liquid alters any moderating effects their availability may have on tobacco cigarette smoking. Daily smokers who are receiving methadone or buprenorphine treatment will be recruited at University of Vermont and Johns Hopkins University. The investigators will study two research cigarettes referred to here as RC1 and 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 EC1 and 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), and biomarkers of tobacco toxicant exposure.

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)

• Number of Cigarettes Smoked 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: Cigarettes with varying nicotine content

RC 2 only

EXPERIMENTAL

Research Cigarettes #2

Other: Cigarettes with varying nicotine content

RC 2 + EC 1

EXPERIMENTAL

Research Cigarettes #2 plus E-cigarettes #1

Other: Cigarettes with varying nicotine content; Other: E-Cigarettes

RC 2 + EC 2

EXPERIMENTAL

Research Cigarettes #2 plus E-cigarettes #2

Other: Cigarettes with varying nicotine content; Other: E-Cigarettes

Interventions

Cigarettes with varying nicotine content 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: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Maintained on opioid medication
• to 70 years old

You may not qualify if:

• Not maintained on opioid medication
• Under 21 years old
• Over 70 years old

Sponsors & Collaborators

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

Study Sites (2)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Shirley Plucinski

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

Tobacco Products; 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: Stacey C. Sigmon, PhD
• Organization: University of Vermont

stacey.sigmon@uvm.edu

802-656-9987

Study Officials

• Stacey C. Sigmon, Ph.D.

  University of Vermont

  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 17, 2019
• Study Start: October 18, 2020
• Primary Completion: November 27, 2023
• Study Completion: November 27, 2023
• Last Updated: March 30, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (2)