Tobacco DependenceNCT03625986
Does Switching to Nicotine Containing Electronic Cigarettes Reduce Health Risk Markers
A study testing Nicotine-Containing Electronic Cigarette and Non-Nicotine Electronic Cigarette in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Dependence
- What is being tested?
- Nicotine-Containing Electronic Cigarette and Non-Nicotine Electronic Cigarette
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Apr 2022to 23 Feb 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 21 to 70
- Smoke ≥5 cigarettes per day for at least the past 12 months
- Smoke regular, filtered cigarettes or machine-rolled cigarettes with a filter
- Exhaled CO measurement ≥6 ppm at baseline visit
- No serious quit attempt in prior month
- Willing to completely cease cigarette consumption and switch to an e-cig
Show all 9Show fewer
- Willing and able to attend regular visits over a 7-week period
- Able to read and write in English
- Able to understand and consent to study procedures
Who cannot join
- Unstable or significant medical condition such as COPD, kidney disease, or liver disease in the past 12 months
- Severe immune system disorders
- Women who are pregnant, trying to become pregnant, or nursing
- Use of any non-cigarette nicotine delivery product in the past 7 days
- Use of an e-cig for 5 or more days in the past 28 days or any use in the past 7 days
- Uncontrolled mental illness or substance abuse or inpatient treatment for these conditions in the past 6 months
Show all 14Show fewer
- History of a seizure disorder or had a seizure in the past 12 months
- Currently or have ever 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.
- History of difficulty providing or unwilling to provide blood samples (fainting, poor veins, anxiety, seizures)
- Surgery requiring general anesthesia in the past 6 weeks
- Use of marijuana or any illicit drug/prescription drugs for non-medical use daily/almost daily or weekly in the past 3 months per NIDA Quick Screen
- Use of hand-rolled, roll your own cigarettes
- Known allergy to propylene glycol or vegetable glycerin
- Other member of household currently participating in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
The Pennsylvania State University College of Medicine
Hershey, Pennsylvania, 17033
About this study
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).
Read the detailed description
This project is a prospective parallel-group randomized double-blind, placebo-controlled study in which 104 current smokers who are willing to completely switch from their regular cigarettes to an electronic cigarette (SREC) for 6 weeks will be randomly allocated to use a SREC containing either 58 or 0 mg/ml nicotine in the liquid.
Following randomization to their assigned study product, participants will be supported in their switching efforts with regular contacts both in person at the Penn State Milton S. Hershey Medical Center and over the phone. The main measures will be recorded at two in-person visits after the randomization (switching) visit: (a) 3 weeks after switching and (b) 6 weeks after switching. All participants will also be followed up at 10 weeks by phone to identify whether they have continued to use electronic cigarettes or regular cigarettes and to assess their motivation to change.
- Conditions
- Tobacco Dependence
- Being tested
- Nicotine-Containing Electronic Cigarette, Non-Nicotine Electronic Cigarette
- Keywords
- smoking, electronic cigarettes, nicotine, ecig
- Medical subject headings
- Tobacco Use Disorder, Smoking, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine-Containing Electronic CigaretteOther
Also called 58 mg/mL Nicotine Content SREC
The electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir ("pod") and a rechargeable power supply unit. The experimental group in this project will receive a SREC device with liquid containing 58 mg/mL of nicotine.
Non-Nicotine Electronic CigaretteOther
Also called 0 mg/mL Nicotine Content SREC
The electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir ("pod") and a rechargeable power supply unit. The placebo group in this project will receive a SREC device with liquid containing 0 mg/mL of nicotine.
| Study group | Role | What they receive |
|---|---|---|
| Nicotine-Containing Electronic Cigarette | Experimental | The experimental group will be provided with and encouraged to use a Standardized Research Electronic Cigarette (SREC) with liquid containing 58 mg/ml nicotine for the duration of 6 weeks. Receives: Other: Nicotine-Containing Electronic Cigarette |
| Non-Nicotine Electronic Cigarette | Placebo comparator | The placebo group will be provided with and encouraged to use a Standardized Research Electronic Cigarette (SREC) with liquid containing 0 mg/ml nicotine for the duration of 6 weeks. Receives: Other: Non-Nicotine Electronic Cigarette |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary NNAL Concentration
Concentration of urinary carcinogen biomarker of exposure, NNAL, corrected for creatinine
Measured: 6-week visit (post-treatment)
Secondary outcomes (16)
Pulmonary Function
Forced expiratory volume in one second (FEV1).
Measured: 6-week visit (post-treatment)
Exhaled Carbon Monoxide (CO)
Exhaled CO (parts per million [ppm])
Measured: 6-week visit (post-treatment)
Urine Cotinine Concentration
Cotinine (ng/ml) will serve as a measure of exposure to nicotine.
Measured: 6-week visit (post-treatment)
Blood Pressure
systolic blood pressure in mm Hg
Measured: 6-week visit (post-treatment)
Fagerstrom Test for Nicotine Dependence Mean Total Score
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).
Measured: 6-week visit (post-treatment)
Penn State Electronic Cigarette Dependence Index
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).
Measured: 6-week visit (post-treatment)
Cigarettes Per Day
Mean number of cigarettes smoked per day based on the past 7 days
Measured: 6-week visit (post-treatment)
Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs)
Zero cigarettes or other tobacco products (not including e-cigs) used in the past 7 days and a CO <6ppm
Measured: 6-week visit (post-treatment)
Total Score on Minnesota Nicotine Withdrawal Scale
Withdrawal and craving will be assessed via the Minnesota Nicotine Withdrawal Scale. Total scores range from 0-28. Higher scores indicate worse withdrawal symptoms.
Measured: 1-week visit (post-treatment)
Cigarettes Per Day
Mean number of cigarettes smoked per day based on the past 7 days
Measured: 10-week visit (post-treatment)
E-cig Use Days
The number of days the e-cig was used since 6-week visit (post-treatment)
Measured: 10-week visit (post-treatment)
Number of Participants With Self-reported Abstinence
Abstinence will be considered zero cigarettes and other tobacco products (not including e-cigs) in the past 7 days
Measured: 10-week visit (post-treatment)
Heart Rate Variability (HRV)
Heart Rate Variability (HRV) will be assessed from resting Holter EKG output.
Measured: 6-week visit (post-treatment)
Presence of Premature Ventricular Contractions (PVCs)
Presence of PVCs will be assessed from resting Holter EKG output.
Measured: 6-week visit (post-treatment)
ST-Elevation
ST-Elevation will be assessed from resting Holter EKG output
Measured: 6-week visit (post-treatment)
QRS Duration
QRS duration will be assessed from resting Holter EKG output.
Measured: 6-week visit (post-treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start22 Apr 2022
- Primary completion26 Jan 2024
- Study completion23 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tobacco DependenceStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Jonathan Foulds, Milton S. Hershey Medical Center
- Investigators
- Jonathan Foulds, PhD, Principal investigator, The Pennsylvania State University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03625986
- Sponsor's protocol ID
- 8948
- Other IDs
- U01DA045517
- Status last verified
- Mar 2025
- First submitted
- 2 Aug 2018
- Last updated
- 27 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yingst JM, Krebs NM, Dahal S, Allen SI, Livelsberger C, Peters V, Salkin A, Bordner C, Mazhar L, Reinhart L, Trushin N, Zimmerman C, Hassan K, Bitzer Z, Sciamanna C, Zhu J, Foulds J. Toxicant Exposures After Switching From Cigarettes to a Pod-Based Electronic Cigarette: A Randomized Clinical Trial. JAMA Netw Open. 2026 May 1;9(5):e2613292. doi: 10.1001/jamanetworkopen.2026.13292.
PubMed 42154468
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Switching to Nicotine Containing Electronic Cigarettes Reduce Health Risk Markers
- ClinicalTrials.gov ID
- NCT03625986
- Acronym / sponsor ID
- 8948
- Conditions
- Tobacco Dependence
- Keywords
- smoking, electronic cigarettes, nicotine, ecig
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 22 Apr 2022 (actual)
- Primary completion
- 26 Jan 2024 (actual)
- Study completion
- 23 Feb 2024 (actual)
- First posted
- 10 Aug 2018 (actual)
- Results
- Posted 27 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This project is a prospective parallel-group randomized double-blind, placebo-controlled study in which 104 current smokers who are willing to completely switch from their regular cigarettes to an electronic cigarette (SREC) for 6 weeks will be randomly allocated to use a SREC containing either 58 or 0 mg/ml nicotine in the liquid.
Following randomization to their assigned study product, participants will be supported in their switching efforts with regular contacts both in person at the Penn State Milton S. Hershey Medical Center and over the phone. The main measures will be recorded at two in-person visits after the randomization (switching) visit: (a) 3 weeks after switching and (b) 6 weeks after switching. All participants will also be followed up at 10 weeks by phone to identify whether they have continued to use electronic cigarettes or regular cigarettes and to assess their motivation to change.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nicotine-Containing Electronic Cigarette | Experimental | Other: Nicotine-Containing Electronic CigaretteThe experimental group will be provided with and encouraged to use a Standardized Research Electronic Cigarette (SREC) with liquid containing 58 mg/ml nicotine for the duration of 6 weeks. |
| Non-Nicotine Electronic Cigarette | Placebo comparator | Other: Non-Nicotine Electronic CigaretteThe placebo group will be provided with and encouraged to use a Standardized Research Electronic Cigarette (SREC) with liquid containing 0 mg/ml nicotine for the duration of 6 weeks. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 21 to 70
- Smoke ≥5 cigarettes per day for at least the past 12 months
- Smoke regular, filtered cigarettes or machine-rolled cigarettes with a filter
- Exhaled CO measurement ≥6 ppm at baseline visit
- No serious quit attempt in prior month
Key exclusion criteria (14 listed)
- Unstable or significant medical condition such as COPD, kidney disease, or liver disease in the past 12 months
- Severe immune system disorders
- Women who are pregnant, trying to become pregnant, or nursing
- Use of any non-cigarette nicotine delivery product in the past 7 days
- Use of an e-cig for 5 or more days in the past 28 days or any use in the past 7 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotine-Containing Electronic CigaretteAlso: 58 mg/mL Nicotine Content SRECThe electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir ("pod") and a rechargeable power supply unit. The experimental group in this project will receive a SREC device with liquid containing 58 mg/mL of nicotine. | Other | Nicotine-Containing Electronic Cigarette |
| Non-Nicotine Electronic CigaretteAlso: 0 mg/mL Nicotine Content SRECThe electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir ("pod") and a rechargeable power supply unit. The placebo group in this project will receive a SREC device with liquid containing 0 mg/mL of nicotine. | Other | Non-Nicotine Electronic Cigarette |
Primary outcome
Urinary NNAL Concentration
Time frame: 6-week visit (post-treatment)
Concentration of urinary carcinogen biomarker of exposure, NNAL, corrected for creatinine
16 secondary outcomes
Pulmonary Function
Time frame: 6-week visit (post-treatment)
Exhaled Carbon Monoxide (CO)
Time frame: 6-week visit (post-treatment)
Urine Cotinine Concentration
Time frame: 6-week visit (post-treatment)
Blood Pressure
Time frame: 6-week visit (post-treatment)
Fagerstrom Test for Nicotine Dependence Mean Total Score
Time frame: 6-week visit (post-treatment)
Penn State Electronic Cigarette Dependence Index
Time frame: 6-week visit (post-treatment)
Cigarettes Per Day
Time frame: 6-week visit (post-treatment)
Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs)
Time frame: 6-week visit (post-treatment)
Total Score on Minnesota Nicotine Withdrawal Scale
Time frame: 1-week visit (post-treatment)
Cigarettes Per Day
Time frame: 10-week visit (post-treatment)
E-cig Use Days
Time frame: 10-week visit (post-treatment)
Number of Participants With Self-reported Abstinence
Time frame: 10-week visit (post-treatment)
Heart Rate Variability (HRV)
Time frame: 6-week visit (post-treatment)
Presence of Premature Ventricular Contractions (PVCs)
Time frame: 6-week visit (post-treatment)
ST-Elevation
Time frame: 6-week visit (post-treatment)
QRS Duration
Time frame: 6-week visit (post-treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42154468Yingst JM, Krebs NM, Dahal S, Allen SI, Livelsberger C, Peters V, Salkin A, Bordner C, Mazhar L, Reinhart L, Trushin N, Zimmerman C, Hassan K, Bitzer Z, Sciamanna C, Zhu J, Foulds J. Toxicant Exposures After Switching From Cigarettes to a Pod-Based Electronic Cigarette: A Randomized Clinical Trial. JAMA Netw Open. 2026 May 1;9(5):e2613292. doi: 10.1001/jamanetworkopen.2026.13292.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Foulds, PhD principal investigator
The Pennsylvania State University College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nicotine-Containing Electronic Cigarette and Non-Nicotine Electronic Cigarette in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urinary NNAL Concentration (time frame: 6-week visit (post-treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03625986, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2025.