N/A
N=80
Low Nicotine Cigarettes Plus Electronic Cigarettes
Tobacco Dependence
Bottom Line
View on ClinicalTrials.gov: NCT04058717 ↗Enrolled (actual)
80
Serious AEs
13.8%
Results posted
Sep 2025
Primary outcome: Primary: Urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) — 505.6; 459.1; 373.3; 180.5 pg/mg creatinine — p=0.017
Study Design & Population
- Study type
- Interventional
- Phase
- N/A
- Interventions
- Normal Nicotine Content research cigarettes (Other); High Nicotine e-cigarette (Other); Very Low Nicotine Content research cigarettes (Other); Zero Nicotine e-cigarette (Other)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- Milton S. Hershey Medical Center
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) |
505.6; 459.1; 373.3; 180.5 | 0.017 sig |
| SECONDARY Exhaled Carbon Monoxide |
23.6; 25.2; 21.9; 12.6 | 0.056 |
| SECONDARY Kessler-6 Score |
6.9; 5.7; 5.4; 5.9 | 0.74 |
| SECONDARY Penn State Cigarette Dependence Index |
11.9; 11.5; 11.8; 9.4 | 0.248 |
| SECONDARY Penn State Electronic Cigarette Dependence Index |
3.1; 5.8; 8.1; 5.8 | 0.025 sig |
| SECONDARY Cigarette Abstinence |
1; 1; 4; 4 | 0.289 |
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).
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04058717). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.