Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder

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), biomarkers of tobacco toxicant exposure, brain function and structure, and airway inflammation (fractional nitric oxide concentration in exhaled breath [FeNO]).

Study Overview

• Status: Active, not recruiting
• Conditions: Tobacco Use Disorder
• Intervention / Treatment: Other: E-Cigarettes; Other: Cigarettes with varying nicotine content

• Study Type: Interventional
• Enrollment (Estimated): 310
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shirley Plucinski; Phone Number: 9788752361; Email: shirley.plucinski@uvm.edu

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Maintained on opioid medication
• 21 to 70 years old

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC 1 only; Research Cigarettes #1	Other: Cigarettes with varying nicotine content; 1) Altering the nicotine content of the tobacco research cigarette
Experimental: RC 2 only; Research Cigarettes #2	Other: Cigarettes with varying nicotine content; 1) Altering the nicotine content of the tobacco research cigarette
Experimental: RC 2 + EC 1; Research Cigarettes #2 plus E-cigarettes #1	Other: E-Cigarettes; 1) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition; Other: Cigarettes with varying nicotine content; 1) Altering the nicotine content of the tobacco research cigarette
Experimental: RC 2 + EC 2; Research Cigarettes #2 plus E-cigarettes #2	Other: E-Cigarettes; 1) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition; Other: Cigarettes with varying nicotine content; 1) Altering the nicotine content of the tobacco research cigarette

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: Stacey C. Sigmon, Ph.D., University of Vermont

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2019
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): January 1, 2024

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): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Nicotine Dependence; Affective Disorders; Biomarkers of Exposure; Compensatory Smoking; Reduced Nicotine Cigarettes; Tobacco Withdrawal; Vulnerable Populations; E-Cigarettes
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Tobacco Use Disorder; Opioid-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: CHRMS19-0130; U54DA036114-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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