Tobacco Use Disorder
Conditions
Keywords
Smoking Cessation, Nicotine Free Cigarettes
Brief summary
The purpose of this study is to evaluate the effect of a combination of the 21 mg nicotine patch and very low nicotine content (VLNC) cigarettes compared to 21 mg nicotine patch only and very low nicotine content cigarette only on abstinence, time to relapse and toxicant levels. The study will determine if adding nicotine replacement medication to the very low content cigarettes (VLNC) will augment treatment compared to nicotine patch only or to very low nicotine content cigarettes only.
Detailed description
The purpose of this study is to evaluate the effect of a combination of the 21 mg nicotine patch and very low nicotine content cigarette (VLNC) compared to the VLNC cigarette alone or 21 mg nicotine patch alone on abstinence, time to relapse and toxicant levels. The following primary hypothesis will be tested: Abstinence rates will be highest and the time to relapse will be the longest in the VLNC cigarettes plus nicotine patch condition compared to nicotine patch or VLNC cigarettes alone. Other hypotheses include: 1. Greater positive subjective responses to cigarettes will be observed with VLNC cigarettes plus patch vs. VLNC cigarette; 2. Less drop-outs will be observed in the VLNC plus patch vs the other two conditions; and 3. Less compensatory smoking will be observed in the VLNC plus patch condition compared to VLNC cigarette alone condition. Cigarette smokers will be randomized to: 1. VLNC cigarettes (which provide sensory behavioral aspects of smoking but with limited nicotine) plus nicotine patch for 6 weeks; 2. Nicotine patch for 6 weeks; or 3. VLNC cigarettes alone. Outcome measures will include cessation assessed at the end of treatment as the primary endpoint and at 36 weeks post-treatment, time to lapse and relapse to usual brand cigarettes, and biomarkers of toxicant exposure. Predictors of abstinence and treatment response for each of the treatment conditions will be explored.
Interventions
DRUGNicotine Patch
21 mg
OTHERVLNC Cigarette
Cigarette where the tobacco contains \<0.1 mg of nicotine yield.
OTHERVLNC Cigarette Plus Nicotine Patch
21 mg nicotine patch plus use of cigarette with tobacco containing \<0.1 mg nicotine yield.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* a) Smoking at least 10 cigarettes daily for the past year; * b) In good physical health; * c) No contraindications for medicinal nicotine; and * d) Stable, good mental health.
Exclusion criteria
* a) Subjects must not be using other tobacco or nicotine products. * b) Female subjects cannot be pregnant or nursing and must be using appropriate birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| End of Treatment Abstinence Rate | 12 week | Cotinine and carbon monoxide (CO) verified point prevalence abstinence |
| End of Follow-up Abstinence Rates | 36 weeks | CO- and cotinine-verified point prevalence abstinence |
Secondary
| Measure | Time frame |
|---|---|
| Exposure to Tobacco Toxicants | 6 weeks |
| Time to Lapse or Relapse to Tobacco Use | 26 weeks |
Countries
United States
Participant flow
Recruitment details
Oct 2008 to September 2011 Location was at the University of Minnesota Twin Cities and Duluth, Minnesota
Pre-assignment details
After signing consent and before randomization to groups, 44 were lost to follow-up, 17 were ineligible, 10 were no longer interested, 10 were family members of enrollees.
Participants by arm
| Arm | Count |
|---|---|
| VLNC Cigarette Very Low Nicotine Content Cigarettes : Cigarette where the tobacco contains \<0.1 mg of nicotine yield. | 79 |
| VLNC Cigarette Plus Nicotine Patch VLNC Cigarette Plus Nicotine Patch: 21 mg nicotine patch plus use of cigarette with tobacco containing \<0.1 mg nicotine yield. | 76 |
| Nicotine Patch 21 mg nicotine patch | 80 |
| Total | 235 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 5 | 4 | 3 |
| Overall Study | Lost to Follow-up | 20 | 14 | 16 |
| Overall Study | Physician Decision | 3 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 9 | 3 | 11 |
Baseline characteristics
| Characteristic | VLNC Cigarette Plus Nicotine Patch | Nicotine Patch | VLNC Cigarette | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 76 Participants | 75 Participants | 225 Participants |
| Age, Continuous | 47.0 years STANDARD_DEVIATION 11.9 | 47.3 years STANDARD_DEVIATION 11 | 46.5 years STANDARD_DEVIATION 12.2 | 47.0 years STANDARD_DEVIATION 11.7 |
| Region of Enrollment United States | 76 participants | 80 participants | 79 participants | 235 participants |
| Sex: Female, Male Female | 43 Participants | 46 Participants | 47 Participants | 136 Participants |
| Sex: Female, Male Male | 33 Participants | 34 Participants | 32 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 60 / 79 | 56 / 76 | 54 / 80 |
| serious Total, serious adverse events | 0 / 79 | 0 / 76 | 0 / 80 |
Outcome results
Primary
End of Follow-up Abstinence Rates
CO- and cotinine-verified point prevalence abstinence
Time frame: 36 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VLNC Cigarette | End of Follow-up Abstinence Rates | 14 participants |
| VLNC Cigarette Plus Nicotine Patch | End of Follow-up Abstinence Rates | 15 participants |
| Nicotine Patch | End of Follow-up Abstinence Rates | 15 participants |
Primary
End of Treatment Abstinence Rate
Cotinine and carbon monoxide (CO) verified point prevalence abstinence
Time frame: 12 week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VLNC Cigarette | End of Treatment Abstinence Rate | 19 participants |
| VLNC Cigarette Plus Nicotine Patch | End of Treatment Abstinence Rate | 18 participants |
| Nicotine Patch | End of Treatment Abstinence Rate | 19 participants |
Secondary
Exposure to Tobacco Toxicants
Time frame: 6 weeks
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| VLNC Cigarette | Exposure to Tobacco Toxicants | Total Nicotine Exposure (TNE) | 6.89 pmol/mg creatinine |
| VLNC Cigarette | Exposure to Tobacco Toxicants | Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-buta | 0.40 pmol/mg creatinine |
| VLNC Cigarette | Exposure to Tobacco Toxicants | Cotinine | 2.03 pmol/mg creatinine |
| VLNC Cigarette Plus Nicotine Patch | Exposure to Tobacco Toxicants | Total Nicotine Exposure (TNE) | 27.39 pmol/mg creatinine |
| VLNC Cigarette Plus Nicotine Patch | Exposure to Tobacco Toxicants | Cotinine | 7.65 pmol/mg creatinine |
| VLNC Cigarette Plus Nicotine Patch | Exposure to Tobacco Toxicants | Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-buta | 0.26 pmol/mg creatinine |
| Nicotine Patch | Exposure to Tobacco Toxicants | Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-buta | 0.25 pmol/mg creatinine |
| Nicotine Patch | Exposure to Tobacco Toxicants | Cotinine | 5.50 pmol/mg creatinine |
| Nicotine Patch | Exposure to Tobacco Toxicants | Total Nicotine Exposure (TNE) | 23.10 pmol/mg creatinine |
Secondary
Time to Lapse or Relapse to Tobacco Use
Time frame: 26 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VLNC Cigarette | Time to Lapse or Relapse to Tobacco Use | 2.6 weeks |
| VLNC Cigarette Plus Nicotine Patch | Time to Lapse or Relapse to Tobacco Use | 7.1 weeks |
| Nicotine Patch | Time to Lapse or Relapse to Tobacco Use | 2.1 weeks |