Smoking Cessation
Conditions
Keywords
Smoking Cessation, Cigarette Smoking, Meclizine, Nicotine Patch
Brief summary
The purpose of this study is to evaluate whether meclizine, an antihistamine used to prevent or treat motion sickness, can help smokers quit smoking. This study will also investigate the potential relationship between genes you have inherited and success in quitting smoking.
Interventions
DRUGMeclizine
Pre-Quit Period: In this group, participants will take meclizine daily during the three week pre-quit period. The meclizine will be taken in two doses daily, one capsule with breakfast and one with dinner.
DRUGNicotine Patch
Pre-Quit Period: During weeks two and three, participants will apply active 21mg/24h nicotine patches daily. Post-Quit Period: Following the quit-day these participants will apply active nicotine patches daily using the following dose schedule: 21mg/24h for four weeks, 14mg/24h for one week, and 7mg/24h for one week.
DRUGPlacebo
Pre-Quit Period: In this group, participants will take placebo capsules daily during the three week pre-quit period. The placebo will be taken in two doses daily, one capsule with breakfast and one with dinner.
Sponsors
Philip Morris USA, Inc.
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have no known serious medical conditions; * Are 18-65 years old; * Smoke an average of at least 10 cigarettes per day; * Have smoked at least one cumulative year; * Have an afternoon expired air carbon monoxide (CO) reading of at least 10ppm; * Express a desire to quit smoking in the next thirty days. * Potential subjects must agree to use acceptable contraception during their participation in this study. Potential subjects must agree to avoid the following during their participation in this study: * participation in any other nicotine-related modification strategy outside of this protocol; * use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco; * use of experimental (investigational) drugs or devices; * use of illegal drugs; * use of opiate medications * use of anti-histamines; * use of alcohol (during first three weeks of study participation).
Exclusion criteria
* Inability to attend all required experimental sessions; * Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100. * Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg). * Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety. * Coronary heart disease; * Lifetime history of heart attack; * Cardiac rhythm disorder (irregular heart rhythm); * Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source); * Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure); * History of skin allergy; * Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds); * Liver or kidney disorder (except kidney stones, gallstones); * Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn; * Active ulcers in the past 30 days; * Currently symptomatic lung disorder/disease (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma); * Brain abnormality (including but not limited to stroke, brain tumor, head injury and seizure disorder); * Migraine headaches that occur more frequently than once per week; * Recent, unexplained fainting spells; * Problems giving blood samples; * Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%); * Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer); * Other major medical condition; * Current psychiatric disease (with the exception of anxiety disorders, obsessive compulsive disorder (OCD) and ADHD); * Current depression; * Bulimia or anorexia; * Pregnant or nursing; * Smokes more than one cigar a month; * Regular alcohol use; * Significant adverse reaction to nicotine patches or meclizine in the past. * Current participation or recent participation (in the past 30 days) in another smoking study at our center or another research facility. * Current participation in another research study. Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive), * Experimental (investigational) drugs; * Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes; * Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine replacement therapy or any other smoking cessation aid. Use (within the past 14 days) of: * Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed); * Benzodiazepines, antihistamines or other drugs with significant sedating or anticholinergic activity that may interact with meclizine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 1 | After 1 week of treatment (relative to baseline) | To evaluate the effects of meclizine alone on ad lib smoking, the percent decrease in expired air carbon monoxide (CO) at the end of week 1 (relative to baseline) will be compared (using ANOVA) between each meclizine group and placebo. |
| Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 3 | After 3 weeks of treatment (relative to baseline) | To evaluate the effects of meclizine as an augmentation treatment in conjunction with nicotine patch, the percent decrease in expired air carbon monoxide (CO) at the end of week 3 (relative to baseline) will be compared (using ANOVA) between each meclizine group and placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Completing the Continuous 4 Week Abstinence From Smoking | weeks 3-6 post quit date | Continuous 4 week abstinence from smoking (weeks 3-6 post quit date), based on self-reported abstinence confirmed by expired air CO ≤8ppm, will be compared between each meclizine group and placebo, using logistic regression analyses |
| Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | After 1 week of treatment (relative to baseline) | To further validate the association between a decrease in expired air CO before the quit date and subsequent abstinence, the decrease in expired air CO from baseline to week 1 (Session P2) will be compared between abstinent and non-abstinent smokers, using ANOVA. |
| Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | After 3 weeks of treatment (relative to baseline) | To further validate the association between a decrease in expired air CO before the quit date and subsequent abstinence, the decrease in expired air CO from baseline to week 3 (Session P3) will be compared between abstinent and non-abstinent smokers, using ANOVA. |
Countries
United States
Participant flow
Recruitment details
Recruitment began on 9/16/11 and ended on 11/30/12. Of the 146 subjects consented during this period, 72 were in our Charlotte, NC office, 45 were in our Durham, NC office and 29 were in our Raleigh, NC office. Of the 146 subjects consented during this study only 75 subjects met all study criteria and were assigned to a study arm.
Participants by arm
| Arm | Count |
|---|---|
| Control Subjects in this group will take placebo meclizine daily for the three weeks prior to their quit date. Subjects will also apply a 21mg/24h nicotine patch daily starting in the second week of pre-quit treatment. Placebo meclizine will be administered in two doses each day.
Nicotine patches: Pre-Quit Period: During weeks two and three, participants will apply active 21mg/24h nicotine patches daily.
Post-Quit Period: Following the quit-day these participants will apply active nicotine patches daily using the following dose schedule: 21mg/24h for four weeks, 14mg/24h for one week, and 7mg/24h for one week. | 25 |
| 25mg Meclizine Subjects in this group will take 25mg of meclizine daily for the three weeks prior to their quit date. Subjects will also apply a 21mg/24h nicotine patch daily starting in the second week of pre-quit treatment. Meclizine will be administered in two doses each day.
Meclizine: Pre-Quit Period: In this group, participants will take meclizine daily during the three week pre-quit period. The meclizine will be taken in two doses daily, one capsule with breakfast and one with dinner.
Nicotine patches: Pre-Quit Period: During weeks two and three, participants will apply active 21mg/24h nicotine patches daily.
Post-Quit Period: Following the quit-day these participants will apply active nicotine patches daily using the following dose schedule: 21mg/24h for four weeks, 14mg/24h for one week, and 7mg/24h for one week. | 25 |
| 50mg Meclizine Subjects in this group will take 50mg of meclizine daily for the three weeks prior to their quit date. Subjects will also apply a 21mg/24h nicotine patch daily starting in the second week of pre-quit treatment. Meclizine will be administered in two doses each day.
Meclizine: Pre-Quit Period: In this group, participants will take meclizine daily during the three week pre-quit period. The meclizine will be taken in two doses daily, one capsule with breakfast and one with dinner.
Nicotine patches: Pre-Quit Period: During weeks two and three, participants will apply active 21mg/24h nicotine patches daily.
Post-Quit Period: Following the quit-day these participants will apply active nicotine patches daily using the following dose schedule: 21mg/24h for four weeks, 14mg/24h for one week, and 7mg/24h for one week. | 25 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 8 | 5 |
Baseline characteristics
| Characteristic | Total | Control | 25mg Meclizine | 50mg Meclizine |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants | 25 Participants | 25 Participants | 25 Participants |
| Age, Continuous | 43.67 years STANDARD_DEVIATION 11.47 | 42.80 years STANDARD_DEVIATION 12.3 | 42.40 years STANDARD_DEVIATION 11.6 | 45.80 years STANDARD_DEVIATION 10.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 74 Participants | 25 Participants | 25 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 14 Participants | 11 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 11 Participants | 11 Participants | 11 Participants |
| Region of Enrollment United States | 75 participants | 25 participants | 25 participants | 25 participants |
| Sex: Female, Male Female | 42 Participants | 13 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Male | 33 Participants | 12 Participants | 10 Participants | 11 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 | 14 / 19 | 14 / 23 | 15 / 25 |
| serious Total, serious adverse events | 0 / 19 | 0 / 23 | 0 / 25 |
Outcome results
Primary
Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 1
To evaluate the effects of meclizine alone on ad lib smoking, the percent decrease in expired air carbon monoxide (CO) at the end of week 1 (relative to baseline) will be compared (using ANOVA) between each meclizine group and placebo.
Time frame: After 1 week of treatment (relative to baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 1 | 1.73 percentage change | Standard Error 9.03 |
| 25mg Meclizine | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 1 | -14.11 percentage change | Standard Error 5.86 |
| 50mg Meclizine | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 1 | -.63 percentage change | Standard Error 6.85 |
Primary
Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 3
To evaluate the effects of meclizine as an augmentation treatment in conjunction with nicotine patch, the percent decrease in expired air carbon monoxide (CO) at the end of week 3 (relative to baseline) will be compared (using ANOVA) between each meclizine group and placebo.
Time frame: After 3 weeks of treatment (relative to baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 3 | -34.05 percentage change | Standard Error 11.83 |
| 25mg Meclizine | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 3 | -54.10 percentage change | Standard Error 5.41 |
| 50mg Meclizine | Percentage of Change in Expired Air Carbon Monoxide (CO) at End of Week 3 | -35.60 percentage change | Standard Error 8.72 |
Secondary
Number of Participants Completing the Continuous 4 Week Abstinence From Smoking
Continuous 4 week abstinence from smoking (weeks 3-6 post quit date), based on self-reported abstinence confirmed by expired air CO ≤8ppm, will be compared between each meclizine group and placebo, using logistic regression analyses
Time frame: weeks 3-6 post quit date
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control | Number of Participants Completing the Continuous 4 Week Abstinence From Smoking | 2 participants |
| 25mg Meclizine | Number of Participants Completing the Continuous 4 Week Abstinence From Smoking | 7 participants |
| 50mg Meclizine | Number of Participants Completing the Continuous 4 Week Abstinence From Smoking | 2 participants |
Secondary
Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers
To further validate the association between a decrease in expired air CO before the quit date and subsequent abstinence, the decrease in expired air CO from baseline to week 1 (Session P2) will be compared between abstinent and non-abstinent smokers, using ANOVA.
Time frame: After 1 week of treatment (relative to baseline)
Population: Abstinent (n=2 Control, 7 25mg, 2 50mg) Non-abstinent (n=16 Control, 16 25mg, 23 50mg)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | abstinent | 5.00 percentage change | Standard Error 15 |
| Control | Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | non-abstinent | 1.32 percentage change | Standard Error 10.1 |
| 25mg Meclizine | Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | abstinent | 2.64 percentage change | Standard Error 20.56 |
| 25mg Meclizine | Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | non-abstinent | -17.64 percentage change | Standard Error 5.66 |
| 50mg Meclizine | Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | abstinent | -16.67 percentage change | Standard Error 16.67 |
| 50mg Meclizine | Percentage of Change of CO at End of Week 1 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | non-abstinent | -5.37 percentage change | Standard Error 7.35 |
Secondary
Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers
To further validate the association between a decrease in expired air CO before the quit date and subsequent abstinence, the decrease in expired air CO from baseline to week 3 (Session P3) will be compared between abstinent and non-abstinent smokers, using ANOVA.
Time frame: After 3 weeks of treatment (relative to baseline)
Population: Abstinent (n=2 Control, 7 25mg, 2 50mg) Non-abstinent (n=16 Control, 16 25mg, 23 50mg)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | abstinent | -47.50 percentage change | Standard Error 52.5 |
| Control | Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | non-abstinent | -32.13 percentage change | Standard Error 12.32 |
| 25mg Meclizine | Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | abstinent | -82.77 percentage change | Standard Error 10.23 |
| 25mg Meclizine | Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | non-abstinent | -47.72 percentage change | Standard Error 22.02 |
| 50mg Meclizine | Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | abstinent | -56.76 percentage change | Standard Error 35.55 |
| 50mg Meclizine | Percentage of Change of CO at End of Week 3 When Comparing Abstinent Smokers Versus Non-abstinent Smokers | non-abstinent | -33.38 percentage change | Standard Error 39.74 |