Low Nicotine Cigarettes Plus Electronic Cigarettes

NCT04058717 | Completed Results DMC

• 2 other identifiers: STUDY12579R01DA048428
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Tobacco Dependence

Outcome Measures

Primary Outcomes (1)

• Urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)

  Measure of tobacco-specific nitrosamine

  Week 16

Secondary Outcomes (5)

• Exhaled Carbon Monoxide

  Week 16

• Kessler-6 Score

  Week 16

• Penn State Cigarette Dependence Index

  Week 16

• Penn State Electronic Cigarette Dependence Index

  Week 16

• Cigarette Abstinence

  Week 20

Study Arms (4)

NNC cigarettes + High Nicotine Containing E-cigarette

EXPERIMENTAL

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; Other: High Nicotine e-cigarette

NNC cigarettes + Zero Nicotine Containing E-cigarette

EXPERIMENTAL

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; Other: Zero Nicotine e-cigarette

VLNC cigarettes + High Nicotine Containing E-cigarette

EXPERIMENTAL

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; Other: Very Low Nicotine Content research cigarettes

VLNC cigarettes + Zero Nicotine Containing E-cigarette

EXPERIMENTAL

Participants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid

Other: Very Low Nicotine Content research cigarettes; Other: Zero Nicotine e-cigarette

Interventions

Normal Nicotine Content research cigarettes OTHER

Research cigarettes with 11.6 mg nicotine/cigarette.

NNC cigarettes + High Nicotine Containing E-cigarette; NNC cigarettes + Zero Nicotine Containing E-cigarette

High Nicotine e-cigarette OTHER

E-cigarette containing high nicotine e-liquid

NNC cigarettes + High Nicotine Containing E-cigarette; VLNC cigarettes + High Nicotine Containing E-cigarette

Very Low Nicotine Content research cigarettes OTHER

Research cigarettes with 0.2 mg nicotine/cigarette.

VLNC cigarettes + High Nicotine Containing E-cigarette; VLNC cigarettes + Zero Nicotine Containing E-cigarette

Zero Nicotine e-cigarette OTHER

E-cigarette containing zero nicotine e-liquid

NNC cigarettes + Zero Nicotine Containing E-cigarette; VLNC cigarettes + Zero Nicotine Containing E-cigarette

Eligibility Criteria

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

You may qualify if:

• 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)
• \. 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Nicolle Krebs
• Organization: Penn State College of Medicine

nkrebs@pennstatehealth.psu.edu

7175315673

Study Officials

• Jonathan Foulds, PhD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 2 X 2 factorial design

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 15, 2019
• Study Start: June 1, 2021
• Primary Completion: July 15, 2024
• Study Completion: August 12, 2024
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)