NCT03625986

Does Switching to Nicotine Containing Electronic Cigarettes Reduce Health Risk Markers

Completed NA Results posted Last updated 27 March 2025

What this trial tests

NA trial testing Nicotine-Containing Electronic Cigarette in Tobacco Dependence in 105 participants. Completed in 23 February 2024.

Timeline

22 April 2022

Primary endpoint
26 January 2024

23 February 2024

Quick facts

Lead sponsor	Milton S. Hershey Medical Center
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	other
Enrollment	105
Start date	22 April 2022
Primary completion	26 January 2024
Estimated completion	23 February 2024
Sites	1 location across United States

Drugs / interventions tested

• Nicotine-Containing Electronic Cigarette
• Non-Nicotine Electronic Cigarette

Conditions studied

• Tobacco Dependence — all drugs for Tobacco Dependence →

Sponsor

Milton S. Hershey Medical Center

Who can join

Adults 21 to 70, any sex, with Tobacco Dependence. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Urinary NNAL Concentration Primary · 6-week visit (post-treatment)

Concentration of urinary carcinogen biomarker of exposure, NNAL, corrected for creatinine

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	151.6	± 235.1
Non-Nicotine Electronic Cigarette	338.2	± 270.1

Pulmonary Function Secondary · 6-week visit (post-treatment)

Forced expiratory volume in one second (FEV1).

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	2.7	± 0.8
Non-Nicotine Electronic Cigarette	2.7	± 0.8

Exhaled Carbon Monoxide (CO) Secondary · 6-week visit (post-treatment)

Exhaled CO (parts per million \[ppm\])

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	10.7	± 18.8
Non-Nicotine Electronic Cigarette	13.8	± 11.5

Urine Cotinine Concentration Secondary · 6-week visit (post-treatment)

Cotinine (ng/ml) will serve as a measure of exposure to nicotine.

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	5295.7	± 5123.3
Non-Nicotine Electronic Cigarette	2879.7	± 2481.5

Blood Pressure Secondary · 6-week visit (post-treatment)

systolic blood pressure in mm Hg

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	125.91	± 15.74
Non-Nicotine Electronic Cigarette	124.74	± 12.13

Fagerstrom Test for Nicotine Dependence Mean Total Score Secondary · 6-week visit (post-treatment)

Nicotine dependence for cigarettes will be assessed via the Fagerstrom Test for Nicotine Dependence (FTND), a measure with total scores ranging from 0 (very low dependence) to 10 (very high dependence).

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	3.69	± 2.68
Non-Nicotine Electronic Cigarette	3.2	± 2.24

Penn State Electronic Cigarette Dependence Index Secondary · 6-week visit (post-treatment)

Nicotine dependence for e-cigarettes will be assessed via the Penn State Electronic Nicotine Dependence Index, a measure with total scores ranging from 0 (very low dependence) to 20 (very high dependence).

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	7.21	± 3.68
Non-Nicotine Electronic Cigarette	5.45	± 3.47

Cigarettes Per Day Secondary · 6-week visit (post-treatment)

Mean number of cigarettes smoked per day based on the past 7 days

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	3.78	± 6.75
Non-Nicotine Electronic Cigarette	4.74	± 5.21

Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs) Secondary · 6-week visit (post-treatment)

Zero cigarettes or other tobacco products (not including e-cigs) used in the past 7 days and a CO \<6ppm

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	19
Non-Nicotine Electronic Cigarette	6

Total Score on Minnesota Nicotine Withdrawal Scale Secondary · 1-week visit (post-treatment)

Withdrawal and craving will be assessed via the Minnesota Nicotine Withdrawal Scale. Total scores range from 0-28. Higher scores indicate worse withdrawal symptoms.

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	4.2	± 4.89
Non-Nicotine Electronic Cigarette	6.16	± 5.89

Cigarettes Per Day Secondary · 10-week visit (post-treatment)

Mean number of cigarettes smoked per day based on the past 7 days

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	5.03	± 8.04
Non-Nicotine Electronic Cigarette	6.47	± 6.15

E-cig Use Days Secondary · 10-week visit (post-treatment)

The number of days the e-cig was used since 6-week visit (post-treatment)

Group	Value	95% CI
Nicotine-Containing Electronic Cigarette	6.69	± 10.57
Non-Nicotine Electronic Cigarette	2.88	± 6.84

Adverse events — posted to ClinicalTrials.gov

Time frame: 10 weeks. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nicotine-Containing Electronic Cigarette

Serious: 1/52 (2%)

Deaths: 0/52

Non-Nicotine Electronic Cigarette

Serious: 0/52 (0%)

Deaths: 0/52

Serious adverse events (1 terms)

Reaction	System	Nicotine-Containing Electr…	Non-Nicotine Electronic Ci…
Stroke	Cardiac disorders	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Nicotine-Containing Electr…	Non-Nicotine Electronic Ci…
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Headache	Nervous system disorders	—	—
COVID-19	Infections and infestations	—	—
Anxiety	Psychiatric disorders	—	—
Dizziness	Nervous system disorders	—	—

Most-reported serious reactions: Stroke.

Data from ClinicalTrials.gov NCT03625986 adverse events section.

Sponsor's own description

The overall goal of this project is to understand the likely health effects of cigarette smokers switching to a Standardized Research Electronic Cigarette (SREC) and to assess the role of nicotine delivery on switching and acceptability as well as markers of health outcomes.

Current smokers who meet all eligibility criteria will completely switch from their combustible (regular) cigarettes to an electronic cigarette (SREC) that either contains 58 mg/ml of nicotine or 0 mg/ml of nicotine in the liquid.

The investigators' hypothesis is that attempting to switch to a SREC will result in a reduction in markers of harms to health, as compared with the baseline (smoking) measures. The investigators also hypothesize that nicotine-containing SRECs will facilitate switching from smoking more efficiently than zero nicotine SRECs and will result in a significantly greater improvement in markers of health risk, but will result in higher ratings of dependence on the SREC (as compared to the zero nicotine SREC).

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Electronic cigarettes for smoking cessation.
   Hartmann-Boyce J, Lindson N, Butler AR, McRobbie H, et al · · 2022 · cited 147× · PMID 36384212 · DOI 10.1002/14651858.cd010216.pub7
2. Electronic cigarettes for smoking cessation.
   Lindson N, Butler AR, McRobbie H, Bullen C, et al · · 2024 · cited 94× · PMID 38189560 · DOI 10.1002/14651858.cd010216.pub8
3. Electronic cigarettes for smoking cessation.
   Lindson N, Butler AR, McRobbie H, Bullen C, et al · · 2025 · cited 32× · PMID 39878158 · DOI 10.1002/14651858.cd010216.pub9
4. Toxicant Exposures After Switching From Cigarettes to a Pod-Based Electronic Cigarette: A Randomized Clinical Trial.
   Yingst JM, Krebs NM, Dahal S, Allen SI, et al · · 2026 · PMID 42154468 · DOI 10.1001/jamanetworkopen.2026.13292