Tobacco DependenceNCT04058717
Low Nicotine Cigarettes Plus Electronic Cigarettes
A study testing Normal Nicotine Content research cigarettes, High Nicotine e-cigarette and Very Low Nicotine Content research cigarettes in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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). 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?
- Normal Nicotine Content research cigarettes, High Nicotine e-cigarette and Very Low Nicotine Content research cigarettes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2021to 12 Aug 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
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State College of Medicine
Hershey, Pennsylvania, 17033
About this study
Official title: 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).
Read the 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.
- Conditions
- Tobacco Dependence
- Being tested
- Normal Nicotine Content research cigarettes, High Nicotine e-cigarette, Very Low Nicotine Content research cigarettes, Zero Nicotine e-cigarette
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal Nicotine Content research cigarettesOther
Research cigarettes with 11.6 mg nicotine/cigarette.
High Nicotine e-cigaretteOther
E-cigarette containing high nicotine e-liquid
Very Low Nicotine Content research cigarettesOther
Research cigarettes with 0.2 mg nicotine/cigarette.
Zero Nicotine e-cigaretteOther
E-cigarette containing zero nicotine e-liquid
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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 Receives: Other: Very Low Nicotine Content research cigarettes; Other: Zero Nicotine e-cigarette |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)
Measure of tobacco-specific nitrosamine
Measured: Week 16
Secondary outcomes (5)
Exhaled Carbon Monoxide
Measure of cigarette smoke exposure
Measured: Week 16
Kessler-6 Score
Measure of serious psychological distress. This scale is a brief, self-report tool used to assess psychological distress. Scores range from 0-24, with higher scores indicating greater distress
Measured: Week 16
Penn State Cigarette Dependence Index
Measure of cigarette dependence. This 10-item scale (with scores ranging from 0 to 20) was developed to measure cigarette dependence, where a score of 0 indicates no cigarette dependence and 20 indicates maximum cigarette dependence.
Measured: Week 16
Penn State Electronic Cigarette Dependence Index
Measure of e-cigarette dependence. This 10-item scale (with scores ranging from 0 to 20) was developed to measure e-cigarette dependence, where a score of 0 indicates no cigarette dependence and 20 indicates maximum e-cigarette dependence.
Measured: Week 16
Cigarette Abstinence
No cigarette use in the past 7 days and exhaled carbon monoxide < 6ppm
Measured: Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2019
- Study start1 Jun 2021
- Primary completion15 Jul 2024
- Study completion12 Aug 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.
- Other trials for Tobacco DependenceStudies of the same condition, open and under way.
- 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
- Model description
- 2 X 2 factorial design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 88 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, Penn State College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04058717
- Sponsor's protocol ID
- STUDY12579
- Other IDs
- R01DA048428
- Status last verified
- Aug 2025
- First submitted
- 14 Aug 2019
- Last updated
- 11 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Low Nicotine Cigarettes Plus Electronic Cigarettes in Smokers
- ClinicalTrials.gov ID
- NCT04058717
- Acronym / sponsor ID
- STUDY12579
- Conditions
- Tobacco Dependence
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 15 Jul 2024 (actual)
- Study completion
- 12 Aug 2024 (actual)
- First posted
- 15 Aug 2019 (actual)
- Results
- Posted 11 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
- Model description
- 2 X 2 factorial design
| Arm | Type | Receives |
|---|---|---|
| NNC cigarettes + High Nicotine Containing E-cigarette | Experimental | Other: Normal Nicotine Content research cigarettes, Other: High Nicotine e-cigaretteParticipants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e-cigarette with high nicotine e-liquid. |
| NNC cigarettes + Zero Nicotine Containing E-cigarette | Experimental | Other: Normal Nicotine Content research cigarettes, Other: Zero Nicotine e-cigaretteParticipants are provided with normal nicotine content (NNC) cigarettes (11.6 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid. |
| VLNC cigarettes + High Nicotine Containing E-cigarette | Experimental | Other: High Nicotine e-cigarette, Other: Very Low Nicotine Content research cigarettesParticipants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with high nicotine e-liquid. |
| VLNC cigarettes + Zero Nicotine Containing E-cigarette | Experimental | Other: Very Low Nicotine Content research cigarettes, Other: Zero Nicotine e-cigaretteParticipants are provided with very low nicotine content (VLNC) cigarettes (0.2 mg nicotine/cigarette) plus e-cigarette with zero nicotine e-liquid |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (15 listed)
- 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))
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 |
|---|---|---|
| Normal Nicotine Content research cigarettesResearch cigarettes with 11.6 mg nicotine/cigarette. | Other | NNC cigarettes + High Nicotine Containing E-cigarette, NNC cigarettes + Zero Nicotine Containing E-cigarette |
| High Nicotine e-cigaretteE-cigarette containing high nicotine e-liquid | Other | NNC cigarettes + High Nicotine Containing E-cigarette, VLNC cigarettes + High Nicotine Containing E-cigarette |
| Very Low Nicotine Content research cigarettesResearch cigarettes with 0.2 mg nicotine/cigarette. | Other | VLNC cigarettes + High Nicotine Containing E-cigarette, VLNC cigarettes + Zero Nicotine Containing E-cigarette |
| Zero Nicotine e-cigaretteE-cigarette containing zero nicotine e-liquid | Other | NNC cigarettes + Zero Nicotine Containing E-cigarette, VLNC cigarettes + Zero Nicotine Containing E-cigarette |
Primary outcome
Urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)
Time frame: Week 16
Measure of tobacco-specific nitrosamine
5 secondary outcomes
Exhaled Carbon Monoxide
Time frame: Week 16
Kessler-6 Score
Time frame: Week 16
Penn State Cigarette Dependence Index
Time frame: Week 16
Penn State Electronic Cigarette Dependence Index
Time frame: Week 16
Cigarette Abstinence
Time frame: Week 20
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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
Penn State 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 Normal Nicotine Content research cigarettes, High Nicotine e-cigarette and Very Low Nicotine Content research cigarettes 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 11 inclusion and 15 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 11 Sep 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. 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 11 Sep 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 (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Sep 2025.