Low Nicotine Cigarettes Plus Electronic Cigarettes

Randomized Trial of Low Nicotine Cigarettes Plus Electronic Cigarettes in Smokers

This study aims to determine the health effects of very low nicotine content in cigarettes, in conjunction with the availability of nicotine-containing electronic cigarettes (e-cigs) among smokers with mental health conditions (SMHC).

Study Overview

• Status: Recruiting
• Conditions: Tobacco Dependence
• Intervention / Treatment: Other: Normal Nicotine Content research cigarettes; Other: High Nicotine e-cigarette; Other: Zero Nicotine e-cigarette; Other: Very Low Nicotine Content research cigarettes

Detailed Description

The specific objective of this study is to recruit a cohort of 240 current exclusive daily SMHC (diagnosed using the MINI International Neuropsychiatric Interview) and to measure a comprehensive battery of behavioral and health indicators at 4, 8, 12 and 16 weeks after being randomized to use either normal nicotine content (NNC) Spectrum cigarettes (11.6 mg nicotine/cigarette) or very low nicotine content (VLNC) Spectrum cigarettes (0.2 mg nicotine/cigarette) while also having access to an electronic cigarette (containing either 0 nicotine or high nicotine e-liquid) in a randomized double-blind, placebo-controlled, 2 by 2 design. All participants will be followed up with a study visit 4 weeks after the final randomized visit to identify whether they have continued to use e-cigs/cigarettes and to assess their motivation in smoking abstinence.

Our central hypothesis is that key markers of harms to health (e.g. urinary NNAL, exhaled carbon monoxide, measures of addiction, and mental distress) will be significantly improved among SMHC who are provided VLNC cigarettes and high nicotine e-cigs.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicolle Krebs, MS; Phone Number: 717-531-5673; Email: nkrebs@pennstatehealth.psu.edu
• Study Contact Backup: Name: Jonathan Foulds, PhD; Phone Number: 717-531-3504; Email: jfoulds@psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State College of Medicine
      • Principal Investigator: Jonathan Foulds, PhD
      • Contact: Nicolle M Krebs, MS; Phone Number: 717-531-5673; Email: nkrebs@pennstatehealth.psu.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Smoke >5 cigarettes per day for at least the prior 12 months
• Smoke regular, filtered cigarettes or machine-rolled cigarettes with a filter
• Exhaled CO measurement of ≥ 6 parts per million at baseline
• No serious cigarette smoking quit attempt or use of any FDA-approved smoking cessation medication in the prior 30 days (includes any nicotine replacement, varenicline, bupropion [used specifically as a quitting aid])
• No plans to quit smoking within the next 3 weeks
• Must be willing to both switch to a different type of cigarette that may contain a different amount of nicotine and to try an e-cig to substitute for some of their cigarettes
• Must be willing and able to respond to contacts from study staff or attend visits over the study period (not planning to move, not planning extended vacation, no planned surgeries)
• 9. Must meet lifetime diagnostic criteria for a current or lifetime unipolar or bipolar mood disorder (e.g. major depressive disorder, major depressive episode, manic episode, hypomanic episode, bipolar disorder), an anxiety disorder (e.g. panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, , agoraphobia, social anxiety disorder, generalized anxiety disorder), a psychotic disorder (e.g. mood disorder or other psychotic disorder), or an eating disorder (e.g. anorexia or bulimia) based on the MINI-International Neuropsychiatric Interview Standard (MINI) (version 7.0.2)
• Able to read and write in English
• Able to understand and give informed consent
• Access to a computer/smartphone with e-mail and a reliable internet connection

Exclusion Criteria:

• Women who are pregnant and/or nursing or trying to become pregnant
• Unstable or significant medical condition in the past 3 months (e.g., recent heart attack or other serious heart condition, stroke, severe angina, high blood pressure [systolic >159 mmHg or diastolic >99 mmHg during screening)
• Respiratory diseases (e.g., exacerbations of asthma or COPD, require oxygen, require oral prednisone), kidney (e.g., dialysis) or liver disease (e.g., cirrhosis), severe immune system disorders (e.g., uncontrolled HIV/AIDS, multiple sclerosis symptoms) or any medical disorder/medication that may affect participant safety or biomarker data
• Uncontrolled mental illness or substance abuse, or inpatient treatment for these in the past 6 months
• Current suicide risk on clinical assessment (above "low risk" score (or ≥ 9) on MINI diagnostic interview suicide module during screening (34))
• Use of any non-cigarette nicotine delivery product (e.g., pipe, cigar, dip, chew, snus, hookah, e-cig, strips or sticks, IQOS) in the past 7 days at screening
• Use of an e-cig for 5 or more days in the past 28 days or any use in the past 7 days at screening
• Use of marijuana or other illegal drugs/prescription drugs for non-medical use daily/almost daily or weekly in the past 3 months per NIDA Quick Screen
• Any known allergy to propylene glycol or vegetable glycerin
• Surgery requiring general anesthesia in the past 6 weeks
• Unwilling to remain on one flavor of cigarette (regular or menthol) for the duration of the trial
• Previous use of SPECTRUM research cigarettes in the past 6 months
• Other member of household currently participating in the study
• History of a seizure disorder or had a seizure in the past 12 months
• Currently taking or have taken medications prescribed to prevent seizures (such as Carbamazepine or Phenobarbital). Using seizure medications for off-label use (indications other than treatment for seizures) will not be included as an exclusion, these will be assessed on a case-by-case basis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNC cigarettes + High Nicotine Containing E-cigarette; Participants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e-cigarette with high nicotine e-liquid.	Other: Normal Nicotine Content research cigarettes; Research cigarettes with 11.6 mg nicotine/cigarette.; Other: High Nicotine e-cigarette; E-cigarette containing high nicotine e-liquid
Experimental: NNC cigarettes + Zero Nicotine Containing E-cigarette; Participants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid.	Other: Normal Nicotine Content research cigarettes; Research cigarettes with 11.6 mg nicotine/cigarette.; Other: Zero Nicotine e-cigarette; E-cigarette containing zero nicotine e-liquid
Experimental: VLNC cigarettes + High Nicotine Containing E-cigarette; Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with high nicotine e-liquid.	Other: High Nicotine e-cigarette; E-cigarette containing high nicotine e-liquid; Other: Very Low Nicotine Content research cigarettes; Research cigarettes with 0.2 mg nicotine/cigarette.
Experimental: VLNC cigarettes + Zero Nicotine Containing E-cigarette; Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid	Other: Zero Nicotine e-cigarette; E-cigarette containing zero nicotine e-liquid; Other: Very Low Nicotine Content research cigarettes; Research cigarettes with 0.2 mg nicotine/cigarette.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol)	Measure of tobacco-specific nitrosamine	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exhaled Carbon Monoxide	Measure of cigarette smoke exposure	Week 16
Kessler-6 score	Measure of serious psychological distress	Week 16
Penn State Cigarette Dependence Index	Measure of cigarette dependence	Week 16
Penn State Electronic Cigarette Dependence Index	Measure of e-cigarette dependence	Week 16
Cigarette abstinence	No cigarette use in the past 7 days and exhaled carbon monoxide < 6ppm	Week 20

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Jonathan Foulds, PhD, Penn State College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: August 14, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; 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: STUDY12579; R01DA048428 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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