Nicotine DependenceNCT02139930
Project 2: Strategies for Reducing Nicotine Content in Cigarettes
A study testing Immediate Nicotine Reduction Group and Gradual Nicotine Reduction Group in people with Nicotine Dependence and Tobacco Smoking, run by Wake Forest University Health Sciences at 10 sites in United States.
Trial summary
The main goal of this project is to compare two different approaches to reducing levels of nicotine in cigarettes: an immediate reduction in nicotine content in cigarettes to non-addictive levels or a gradual reduction in nicotine content in cigarettes to non-addictive levels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nicotine Dependence, Tobacco Smoking
- What is being tested?
- Immediate Nicotine Reduction Group and Gradual Nicotine Reduction Group
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,250 participants
- Where
- 10 sitesUnited States
- Study dates
- Sep 2014to 14 Mar 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18+
- Daily smokers who smoke an average of at least five cigarettes per day for at least 1 year
- Breath CO levels > 8 ppm (if ≤ 8 ppm, then NicAlert Strip level must indicate regular smoking)
Who cannot join
- Planned quit date in the next 30 days
- Currently seeking treatment for smoking cessation
- Currently using nicotine replacement therapies or other pharmacotherapies as cessation aid (non-cessation intermittent use acceptable)
- A quit attempt in the past 30 days resulting in greater than 3 days of abstinence
- Using other tobacco products or e-cigarettes more than 9 days in the past 30 days
- Significant unstable medical conditions (Any significant change in a serious medical condition occurring during the past 3 months including, cardiovascular disease, COPD, and cancer, as determined by the licensed medical professional at each site)
Show all 54Show fewer
- Unstable psychiatric conditions (Any significant change in psychiatric symptoms during the past 3 months as determined by the licensed medical professional at each site)
- Schizophrenia and schizoaffective disorder
- Psychiatric medication changes (e.g., new prescriptions, changes in dosages, or discontinuation of medications) in the past 3 months that was a result of negative changes in symptoms.
- Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP
- Marijuana will be tested for but will not be an exclusionary criterion.
- Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded.
- Participants failing the toxicology screen will be allowed to re-screen once.
- Blood alcohol level > 0.01
- Participants failing the blood alcohol screen will be allowed to re-screen once.
- Binge drinking alcohol (more than 9 days in the past 30 days, 4/5 drinks per day (female/male))
- Pregnant, trying to become pregnant or breastfeeding
- Predominant use of 'roll your own cigarettes'
- CO reading >80 ppm
- Systolic BP greater than or equal to 160
- Participants failing for blood pressure will be allowed to re-screen once.
- Diastolic BP greater than or equal to 100
- Participants failing for blood pressure will be allowed to re-screen once.
- Systolic BP below 90 and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
- Participants failing for blood pressure will be allowed to re-screen once.
- Diastolic BP below 50 and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
- Participants failing for blood pressure will be allowed to re-screen once.
- Heart rate greater than or equal to 105 bpm
- Participants failing for heart rate will be allowed to re-screen once.
- Heart rate lower than 45 bpm and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)
- Participants failing for heart rate will be allowed to re-screen once.
- Indicating any suicidal ideation in the past month, suicide attempts in the past 5 years (if within past 5 to 10 years, requires physician approval), or score of >4 on the MINI suicide subscale
- Household member enrolled in the study concurrently.
- Inability to independently read and comprehend the consent form and other written study materials and measures because participants are required to complete parts of the protocol at home independently.
- Participated in prior study that involved reduced nicotine content cigarettes.
- Having participated in a research study during the past three months in a study that would impact baseline smoking or response to study products.
- Currently taking the following anticonvulsant medications:
- Phenytoin [Brand Name: Dilantin]
- Carbamazepine [Brand Name: Tegretol, Carbatrol, Equetro, Epitol]
- Oxcarbazepine [Brand Name: Trileptal]
- Primidone [Brand Name: Mysoline]
- Phenobarbital
- Currently taking the following medication:
- Bendamustine (Treanda)
- Clopidogrel (Plavix)
- Clozapine (Clozaril, FazaClo)
- Erlotinib (Tarceva)
- Flecainide (Tambocor)
- Fluvoxamine (Luvox)
- Irinotecan (Camptosar)
- Olanzapine (Zyprexa)
- Ropinirole (Requip)
- Tacrine (Cognex)
- Theophylline (Theo Dur, etc.)
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Johns Hopkins University
Baltimore, Maryland, 21224
University of Minnesota Medical School Duluth
Duluth, Minnesota, 55812
Duke University
Durham, North Carolina, 27705
Oregon Research Institute
Eugene, Oregon, 97403
MDAnderson Cancer Center
Houston, Texas, 77030
University of Minnesota
Minneapolis, Minnesota, 55455
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mayo Clinic
Phoenix, Arizona, 85054
University of California San Francisco
San Francisco, California, 94143
Moffitt Cancer Center
Tampa, Florida, 33617
About this study
The main goal of this project is to compare two different approaches to reducing levels of nicotine in cigarettes: an immediate reduction in nicotine content in cigarettes to non-addictive levels or a gradual reduction in nicotine content in cigarettes to non-addictive levels. These two approaches will then be contrasted to a group that continues to smoke cigarettes with nicotine content similar to conventional cigarettes.
Read the detailed description
This project will be conducted to compare product use patterns and biomarkers of exposure between smokers who are assigned to a) gradual reduction in reduced nicotine content (RNC) cigarettes; b) immediate reduction to very low nicotine content (VLNC) cigarettes or c) normal nicotine content (NNC) cigarettes. The outcomes from this study will provide information on different approaches to reducing levels of nicotine in cigarettes and will determine the approach with the most optimal outcomes taking into account the balance between overall risk reduction (possibly maximized by abrupt switching) and compliance and acceptability (possibly maximized by gradual reduction of RNC cigarettes).
- Conditions
- Nicotine Dependence, Tobacco Smoking
- Being tested
- Normal Nicotine Control Group, Immediate Nicotine Reduction Group, Gradual Nicotine Reduction Group
- Keywords
- smoking, nicotine reduction
- Medical subject headings
- Tobacco Use Disorder, Tobacco Smoking, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal Nicotine Control GroupBehavioural
Participants will smoke experimental cigarettes for a period of 20-weeks.
Immediate Nicotine Reduction GroupBehavioural
Participants will smoke experimental cigarettes for a period of 20-weeks.
Gradual Nicotine Reduction GroupBehavioural
Participants will smoke experimental cigarettes for a period of 20-weeks.
| Study group | Role | What they receive |
|---|---|---|
| Normal Nicotine Control Group | Active comparator | These subjects will smoke normal nicotine content Spectrum brand cigarettes for 20 weeks. Receives: Behavioral: Normal Nicotine Control Group |
| Immediate Nicotine Reduction Group | Experimental | This group will immediately be switched to smoking very low nicotine content (VLNC) Spectrum brand cigarettes. They will smoke these cigarettes for 20 weeks. Receives: Behavioral: Immediate Nicotine Reduction Group |
| Gradual Nicotine Reduction Group | Experimental | This group will smoke progressively lower nicotine content Spectrum brand cigarettes for a period of one month each until they end up smoking the same VLNC cigarettes as the immediate reduction group. Receives: Behavioral: Gradual Nicotine Reduction Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicant exposure pattern: Expired air carbon monoxide
Between group comparison of expired air carbon monoxide (CO) values at week 20 using baseline CO values as a covariate.
Measured: 20-week treatment period
Toxicant exposure pattern: Urinary phenanthrene tetroal (Phe)
Between group comparison of urinary phenanthrene tetroal values at week 20 using baseline values as a covariate.
Measured: 20-week treatment period
Toxicant exposure pattern: Urinary mercapturic acids of acrolein
Between group comparison of urinary mercapturic acid level at week 20 using baseline values as a covariate.
Measured: 20-week treatment period
Secondary outcomes (8)
Nicotine exposure: Total nicotine equivalents (TNE)
Between group comparison of urinary total nicotine equivalents at week 20 using baseline values as a covariate.
Measured: End of treatment (Week 20)
Other toxicant exposure: Tobacco specific nitrosamines-Total NNAL and NNN
Between group comparison of urinary total NNAL and NNN levels at week 20 using baseline values as a covariate.
Measured: End of treatment (Week 20)
Effect biomarker: C-Reactive protein-high sensitivity as an inflammation biomarker
Between group comparison of C-Reactive protein levels in serum at week 20 using baseline values as a covariate.
Measured: End of treatment (Week 20)
Measure of acceptability: Retention in study
Between group comparison of early termination from the study.
Measured: End of treatment (Week 20)
Measure of acceptability: Non-compliance
Between group comparison of use of non-study tobacco products.
Measured: End of treatment (Week 20)
Effect biomarker: 8-epi-PGF2α as a biomarker for oxidative stress
Between group comparison of 8-epi-PGF2α at week 20 using baseline values as a covariate.
Measured: End of treatment (Week 20)
Effect biomarker: White blood cells count as inflammation biomarker
Between group comparison of white blood cell count at week 20 using baseline values as a covariate.
Measured: End of treatment (Week 20)
Nicotine exposure: Urinary cotinine
Between group comparison of urinary total nicotine equivalents at week 20 using baseline values as a covariate.
Measured: End of treatment (Week 20)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2014 (estimated)
- Study startSep 2014
- Primary completionMar 2017
- Study completion14 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Eric Donny, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02139930
- Sponsor's protocol ID
- U54 DA031659-P2
- Other IDs
- U54DA031659
- Status last verified
- Aug 2018
- First submitted
- 12 May 2014
- Last updated
- 15 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Hatsukami DK, Luo X, Jensen JA, al'Absi M, Allen SS, Carmella SG, Chen M, Cinciripini PM, Denlinger-Apte R, Drobes DJ, Koopmeiners JS, Lane T, Le CT, Leischow S, Luo K, McClernon FJ, Murphy SE, Paiano V, Robinson JD, Severson H, Sipe C, Strasser AA, Strayer LG, Tang MK, Vandrey R, Hecht SS, Benowitz NL, Donny EC. Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial. JAMA. 2018 Sep 4;320(9):880-891. doi: 10.1001/jama.2018.11473.
PubMed 30193275
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Project 2: Strategies for Reducing Nicotine Content in Cigarettes
- ClinicalTrials.gov ID
- NCT02139930
- Acronym / sponsor ID
- U54 DA031659-P2
- Conditions
- Nicotine Dependence, Tobacco Smoking
- Keywords
- smoking, nicotine reduction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,250 participants (estimated)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Sep 2014
- Primary completion
- Mar 2017 (actual)
- Study completion
- 14 Mar 2017 (actual)
- First posted
- 16 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main goal of this project is to compare two different approaches to reducing levels of nicotine in cigarettes: an immediate reduction in nicotine content in cigarettes to non-addictive levels or a gradual reduction in nicotine content in cigarettes to non-addictive levels. These two approaches will then be contrasted to a group that continues to smoke cigarettes with nicotine content similar to conventional cigarettes.
Detailed description
This project will be conducted to compare product use patterns and biomarkers of exposure between smokers who are assigned to a) gradual reduction in reduced nicotine content (RNC) cigarettes; b) immediate reduction to very low nicotine content (VLNC) cigarettes or c) normal nicotine content (NNC) cigarettes. The outcomes from this study will provide information on different approaches to reducing levels of nicotine in cigarettes and will determine the approach with the most optimal outcomes taking into account the balance between overall risk reduction (possibly maximized by abrupt switching) and compliance and acceptability (possibly maximized by gradual reduction of RNC cigarettes).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal Nicotine Control Group | Active comparator | Behavioral: Normal Nicotine Control GroupThese subjects will smoke normal nicotine content Spectrum brand cigarettes for 20 weeks. |
| Immediate Nicotine Reduction Group | Experimental | Behavioral: Immediate Nicotine Reduction GroupThis group will immediately be switched to smoking very low nicotine content (VLNC) Spectrum brand cigarettes. They will smoke these cigarettes for 20 weeks. |
| Gradual Nicotine Reduction Group | Experimental | Behavioral: Gradual Nicotine Reduction GroupThis group will smoke progressively lower nicotine content Spectrum brand cigarettes for a period of one month each until they end up smoking the same VLNC cigarettes as the immediate reduction group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18+
- Daily smokers who smoke an average of at least five cigarettes per day for at least 1 year
- Breath CO levels > 8 ppm (if ≤ 8 ppm, then NicAlert Strip level must indicate regular smoking)
Key exclusion criteria (54 listed)
- Planned quit date in the next 30 days
- Currently seeking treatment for smoking cessation
- Currently using nicotine replacement therapies or other pharmacotherapies as cessation aid (non-cessation intermittent use acceptable)
- A quit attempt in the past 30 days resulting in greater than 3 days of abstinence
- Using other tobacco products or e-cigarettes more than 9 days in the past 30 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 |
|---|---|---|
| Normal Nicotine Control GroupParticipants will smoke experimental cigarettes for a period of 20-weeks. | Behavioural | Normal Nicotine Control Group |
| Immediate Nicotine Reduction GroupParticipants will smoke experimental cigarettes for a period of 20-weeks. | Behavioural | Immediate Nicotine Reduction Group |
| Gradual Nicotine Reduction GroupParticipants will smoke experimental cigarettes for a period of 20-weeks. | Behavioural | Gradual Nicotine Reduction Group |
Primary outcome
Toxicant exposure pattern: Expired air carbon monoxide
Time frame: 20-week treatment period
Between group comparison of expired air carbon monoxide (CO) values at week 20 using baseline CO values as a covariate.
Toxicant exposure pattern: Urinary phenanthrene tetroal (Phe)
Time frame: 20-week treatment period
Between group comparison of urinary phenanthrene tetroal values at week 20 using baseline values as a covariate.
Toxicant exposure pattern: Urinary mercapturic acids of acrolein
Time frame: 20-week treatment period
Between group comparison of urinary mercapturic acid level at week 20 using baseline values as a covariate.
8 secondary outcomes
Nicotine exposure: Total nicotine equivalents (TNE)
Time frame: End of treatment (Week 20)
Other toxicant exposure: Tobacco specific nitrosamines-Total NNAL and NNN
Time frame: End of treatment (Week 20)
Effect biomarker: C-Reactive protein-high sensitivity as an inflammation biomarker
Time frame: End of treatment (Week 20)
Measure of acceptability: Retention in study
Time frame: End of treatment (Week 20)
Measure of acceptability: Non-compliance
Time frame: End of treatment (Week 20)
Effect biomarker: 8-epi-PGF2α as a biomarker for oxidative stress
Time frame: End of treatment (Week 20)
Effect biomarker: White blood cells count as inflammation biomarker
Time frame: End of treatment (Week 20)
Nicotine exposure: Urinary cotinine
Time frame: End of treatment (Week 20)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
- Derived from this study: PubMed 30193275Hatsukami DK, Luo X, Jensen JA, al'Absi M, Allen SS, Carmella SG, Chen M, Cinciripini PM, Denlinger-Apte R, Drobes DJ, Koopmeiners JS, Lane T, Le CT, Leischow S, Luo K, McClernon FJ, Murphy SE, Paiano V, Robinson JD, Severson H, Sipe C, Strasser AA, Strayer LG, Tang MK, Vandrey R, Hecht SS, Benowitz NL, Donny EC. Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial. JAMA. 2018 Sep 4;320(9):880-891. doi: 10.1001/jama.2018.11473.
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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.
Eric Donny, PhD principal investigator
University of Pittsburgh
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immediate Nicotine Reduction Group and Gradual Nicotine Reduction Group in people with Nicotine Dependence and Tobacco Smoking, run by Wake Forest University Health Sciences at 10 sites 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 3 inclusion and 54 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 15 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Toxicant exposure pattern: Expired air carbon monoxide (time frame: 20-week treatment period). The study lists 3 primary outcomes in all. 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 NCT02139930, 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 15 Aug 2018.