Nicotine Dependence
Conditions
Keywords
Nicotine addiction, Smoking Cessation, Quit Smoking, moclobemide, Nicotine Patch
Brief summary
The proposed study will assess the efficacy of moclobemide, a selective, reversible MAO-A inhibitor, in facilitating smoking cessation in treatment-seeking female smokers. This rationale is based on several findings from previous work: 1) cigarette smoke contains constituents that inhibit both forms of the enzyme monoamine oxidase (MAO-A and MAO-B); 2) that severity of depression symptoms after smoking abstinence is correlated with the level of MAO-A inhibition previously obtained from smoking; 3) moclobemide, an MAO-A inhibitor was found efficacious in a smoking cessation treatment trial (Berlin et al., 1995); and 4) women show a greater association between smoking and depression than men and women smokers in our previous trials report smoking to alleviate symptoms of depression to a greater extent than men.
Interventions
DRUGNicotine Patch
Pre-Quit Period: 2 weeks of patch use (21mg/24hr) Post Quit Period: 10 weeks of patch use (21mg/24hr for 6 weeks, 14mg/24hr for 2 weeks, and 7mg/24hr for 2 weeks)
DRUGMoclobemide
Pre-Quit Period: 1 week of moclobemide use (400 mg/day in 2 divided doses) Post Quit Period: 10 weeks of moclobemide use (400 mg/day in 2 divided doses)
Sponsors
Philip Morris USA, Inc.
National Institute on Drug Abuse (NIDA)
Jed E. Rose
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have no known serious medical conditions; * Female; * Are 18-65 years old; * Smoke an average of at least 20 cigarettes per day; * Have smoked at least one cumulative year; * Have a Fagerstrom Test for Nicotine Dependence score of at least 5; * Have an expired air carbon monoxide (CO) reading of at least 10ppm; * Able to read and understand English; * Express a desire to quit smoking in the next thirty days. Potential subjects must agree to avoid the following during their participation in this study: * excessive alcohol consumption; * use of other antidepressants; * general anesthesia; * 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; * cimetidine; * Tyramine rich foods; * use of opiate medications.
Exclusion criteria
* Hypertension; * Hypotension with symptoms; * Coronary heart disease; * Lifetime history of heart attack; * Cardiac rhythm disorder; * Chest pains; * Cardiac (heart) disorder; * Active skin disorder; * Liver or kidney disorder; * Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn; * Active ulcers in the past 30 days; * Currently Symptomatic lung disorder/disease; * Brain abnormality; * Migraine headaches that occur more frequently than once per week; * Recent, unexplained fainting spells; * Problems giving blood samples; * Diabetes (unless controlled by diet and exercise alone); * Current cancer or treatment for cancer in the past six; * Other major medical condition; * Current psychiatric disease; * Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide; * Current depression; * Bulimia or anorexia; * Use (within the past 45 days) of psychiatric medications including antidepressants and anti-psychotics; * Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates), * Experimental (investigational) drugs; * Any medications that are known to affect smoking cessation (e.g. clonidine); * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes; * Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid. * Use of opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed) within the past 14 days; * Smokes more than one cigar a month. * Alcohol abuse; * Significant adverse reaction to nicotine patches, in the past. * Known hypersensitivity to moclobemide or other MAO-A inhibitors. * Current participation or recent participation (in the past 30 days) in another smoking study at our center or another research facility. * Current participation or recent participation (in the past six months) in another medical research study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Continuous Four-week Abstinence From Smoking | Weeks 6-10 post quit day | Number of participants who reported continuous four-week abstinence from smoking (weeks 6-10 post target quit date), confirmed by expired air carbon monoxide (CO). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Point Abstinence From Smoking at Six Months Post Quit | 7 day point abstinence from smoking at six months post quit | Number of participants who reported 7-day point abstinence from smoking at six months post quit, confirmed by expired air CO. |
| Continuous Ten Week Abstinence From Smoking | 10 weeks post quit day | Number of participants who reported continuous ten-week abstinence from smoking (weeks 1-10 post quit day), confirmed by expired air CO. |
| Percentage of Change in Smoking Withdrawal Symptoms | Quit day and 1 week, 3 weeks, 6 weeks, 10 weeks and 6 months post quit day | Withdrawal symptoms will be assessed by questionnaire on Quit Day, 1 week post quit, 3 weeks post quit, 6 weeks post quit,10 weeks post quit and 6 months post quit (if applicable) using the Shiffman-Jarvik questionnaire, which consists of 33-items rated from 1 to 7, where 1= not at all, 2= very little, 3= a little, 4= moderately, 5= a lot, 6= quite a lot, and 7= extremely. The 33 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, Arousal, Somatic - Anxiety, Somatic - G.I., Somatic - Respiratory Tract, and Habit Withdrawal. The range of scores for each subscale will be 1-7, with higher scores indicating more of the withdrawal symptom having been experienced. |
| Percentage of Change in Expired Air Carbon Monoxide (CO) During the First Week of Nicotine Patch Treatment. | Baseline and 1 week | The initial response to nicotine patch will be assessed by looking at the percent change in expired air carbon monoxide (CO) at the end of week one (Study Visit 2) relative to baseline (Study Visit 1). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety of Moclobemide + Nicotine Patch | 1, 2, 4, 7 and 11 weeks after starting Moclobemide + Nicotine Patch | Safety of the moclobemide + nicotine patch treatment will be assessed by tabulating the number of participants rating side effects \> moderate. |
| Tolerability of Moclobemide + Nicotine Patch | 1, 2, 4, 7 and 11 weeks after starting Moclobemide + Nicotine Patch | Tolerability of the moclobemide + nicotine patch treatment will be assessed by tabulating the number of participants requiring dose reductions (or discontinuation of medication). |
Countries
United States
Participant flow
Pre-assignment details
Of the 76 participants who were enrolled, 38 participants attended Study Session 1: 1 participant voluntarily withdrew prior to Study Session 1, 3 participants were lost to contact prior to Study Session 1, and 34 were withdrawn from the study by the PI or medical staff because they did not meet inclusion criteria or met exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Patch+Moclobemide After 1 week of pre-cessation nicotine patch treatment (21 mg/24 h patches), participants will receive moclobemide (400 mg/day in 2 divided doses) for 11 weeks, ending 10 weeks after the target quit date. Nicotine patch treatment will continue at 21 mg/24 h for an additional week prior to the quit date, and then for 6 weeks after the quit date, followed by 14 mg/24 h for 2 weeks and 7 mg/24 h for 2 weeks. All treatment will terminate 10 weeks after the quit date.
Nicotine Patch: Pre-Quit Period: 2 weeks of patch use (21mg/24hr)
Post Quit Period: 10 weeks of patch use (21mg/24hr for 6 weeks, 14mg/24hr for 2 weeks, and 7mg/24hr for 2 weeks)
Moclobemide: Pre-Quit Period: 1 week of moclobemide use (400 mg/day in 2 divided doses)
Post Quit Period: 10 weeks of moclobemide use (400 mg/day in 2 divided doses) | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Withdrawal by Subject | 15 |
Baseline characteristics
| Characteristic | Nicotine Patch+Moclobemide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants |
| Age, Continuous | 46.53 years STANDARD_DEVIATION 9.86 |
| Region of Enrollment United States | 38 participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 37 |
| serious Total, serious adverse events | 0 / 37 |
Outcome results
Primary
Continuous Four-week Abstinence From Smoking
Number of participants who reported continuous four-week abstinence from smoking (weeks 6-10 post target quit date), confirmed by expired air carbon monoxide (CO).
Time frame: Weeks 6-10 post quit day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Patch+Moclobemide | Continuous Four-week Abstinence From Smoking | 7 participants |
Secondary
Continuous Ten Week Abstinence From Smoking
Number of participants who reported continuous ten-week abstinence from smoking (weeks 1-10 post quit day), confirmed by expired air CO.
Time frame: 10 weeks post quit day
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Patch+Moclobemide | Continuous Ten Week Abstinence From Smoking | 4 participants |
Secondary
Percentage of Change in Expired Air Carbon Monoxide (CO) During the First Week of Nicotine Patch Treatment.
The initial response to nicotine patch will be assessed by looking at the percent change in expired air carbon monoxide (CO) at the end of week one (Study Visit 2) relative to baseline (Study Visit 1).
Time frame: Baseline and 1 week
Population: Participants who received Moclobemide.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Patch+Moclobemide | Percentage of Change in Expired Air Carbon Monoxide (CO) During the First Week of Nicotine Patch Treatment. | -18.38 percentage of change | Standard Error 5.551 |
Secondary
Percentage of Change in Smoking Withdrawal Symptoms
Withdrawal symptoms will be assessed by questionnaire on Quit Day, 1 week post quit, 3 weeks post quit, 6 weeks post quit,10 weeks post quit and 6 months post quit (if applicable) using the Shiffman-Jarvik questionnaire, which consists of 33-items rated from 1 to 7, where 1= not at all, 2= very little, 3= a little, 4= moderately, 5= a lot, 6= quite a lot, and 7= extremely. The 33 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, Arousal, Somatic - Anxiety, Somatic - G.I., Somatic - Respiratory Tract, and Habit Withdrawal. The range of scores for each subscale will be 1-7, with higher scores indicating more of the withdrawal symptom having been experienced.
Time frame: Quit day and 1 week, 3 weeks, 6 weeks, 10 weeks and 6 months post quit day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Craving -- % change 1 week from Quit Day | -8.07 percentage of change | Standard Error 7.928 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Craving -- % change 3 weeks from Quit Day | -13.18 percentage of change | Standard Error 4.144 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Craving -- % change 6 weeks from Quit Day | -14.24 percentage of change | Standard Error 4.63 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Craving -- % change 10 weeks from Quit Day | -13.41 percentage of change | Standard Error 6.912 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Craving -- % change 6 months from Quit Day | 23.71 percentage of change | Standard Error 63.69 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Negative Affect -- % change 1 week from Quit Day | -22.82 percentage of change | Standard Error 4.057 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Negative Affect -- % change 3 weeks from Quit Day | -14.26 percentage of change | Standard Error 4.327 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Negative Affect -- % change 6 weeks from Quit Day | -21.53 percentage of change | Standard Error 4.051 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Negative Affect -- % change 10 weeks from Quit Day | -13.92 percentage of change | Standard Error 4.968 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Negative Affect -- % change 6 months from Quit Day | 48.87 percentage of change | Standard Error 65.334 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Appetite -- % change 1 week from Quit Day | -11.40 percentage of change | Standard Error 5.486 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Appetite -- % change 3 weeks from Quit Day | -4.39 percentage of change | Standard Error 7.881 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Appetite -- % change 6 weeks from Quit Day | -17.07 percentage of change | Standard Error 8.819 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Appetite -- % change 10 weeks from Quit Day | 0.73 percentage of change | Standard Error 16.033 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Appetite -- % change 6 months from Quit Day | 27.24 percentage of change | Standard Error 74.446 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Arousal -- % change 1 week from Quit Day | 29.81 percentage of change | Standard Error 8.824 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Arousal -- % change 3 weeks from Quit Day | 29.03 percentage of change | Standard Error 7.004 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Arousal -- % change 6 weeks from Quit Day | 29.99 percentage of change | Standard Error 6.915 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Arousal -- % change 10 weeks from Quit Day | 18.95 percentage of change | Standard Error 6.715 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Arousal -- % change 6 months from Quit Day | 190.88 percentage of change | Standard Error 78.496 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Anxiety -- % change 1 week from Quit Day | -4.65 percentage of change | Standard Error 3.803 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Anxiety -- % change 3 weeks from Quit Day | -5.80 percentage of change | Standard Error 4.788 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Anxiety -- % change 6 weeks from Quit Day | -4.48 percentage of change | Standard Error 5.098 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Anxiety -- % change 10 weeks from Quit Day | -9.44 percentage of change | Standard Error 6.375 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Anxiety -- % change 6 months from Quit Day | -38.79 percentage of change | Standard Error 19.553 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Gastrointestinal -- % change 1 week from Quit Day | -5.80 percentage of change | Standard Error 3.365 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Gastrointestinal -- % change 3 weeks from Quit Day | -2.03 percentage of change | Standard Error 6.602 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Gastrointestinal -- % change 6 weeks from Quit Day | 4.55 percentage of change | Standard Error 16.189 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Gastrointestinal - % change 10 weeks from Quit Day | -12.20 percentage of change | Standard Error 5.1 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Gastrointestinal - % change 6 months from Quit Day | -33.66 percentage of change | Standard Error 18.204 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Respiratory -- % change 1 week from Quit Day | 7.26 percentage of change | Standard Error 6.978 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Respiratory -- % change 3 weeks from Quit Day | 2.06 percentage of change | Standard Error 11.161 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Respiratory -- % change 6 weeks from Quit Day | -5.16 percentage of change | Standard Error 8.628 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Respiratory -- % change 10 weeks from Quit Day | -13.28 percentage of change | Standard Error 8.696 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Respiratory -- % change 6 months from Quit Day | -38.79 percentage of change | Standard Error 19.553 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Habit -- % change 1 week from Quit Day | -9.26 percentage of change | Standard Error 7.272 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Habit -- % change 3 weeks from Quit Day | -11.41 percentage of change | Standard Error 6.309 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Habit -- % change 6 weeks from Quit Day | -12.22 percentage of change | Standard Error 7.705 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Habit -- % change 10 weeks from Quit Day | 1.49 percentage of change | Standard Error 14.642 |
| Nicotine Patch+Moclobemide | Percentage of Change in Smoking Withdrawal Symptoms | Habit -- % change 6 months from Quit Day | -38.79 percentage of change | Standard Error 19.553 |
Secondary
Point Abstinence From Smoking at Six Months Post Quit
Number of participants who reported 7-day point abstinence from smoking at six months post quit, confirmed by expired air CO.
Time frame: 7 day point abstinence from smoking at six months post quit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Patch+Moclobemide | Point Abstinence From Smoking at Six Months Post Quit | 2 participants |
Other Pre-specified
Safety of Moclobemide + Nicotine Patch
Safety of the moclobemide + nicotine patch treatment will be assessed by tabulating the number of participants rating side effects \> moderate.
Time frame: 1, 2, 4, 7 and 11 weeks after starting Moclobemide + Nicotine Patch
Population: Participants who received Moclobemide.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Patch+Moclobemide | Safety of Moclobemide + Nicotine Patch | 21 participants |
Other Pre-specified
Tolerability of Moclobemide + Nicotine Patch
Tolerability of the moclobemide + nicotine patch treatment will be assessed by tabulating the number of participants requiring dose reductions (or discontinuation of medication).
Time frame: 1, 2, 4, 7 and 11 weeks after starting Moclobemide + Nicotine Patch
Population: Participants who received Moclobemide.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nicotine Patch+Moclobemide | Tolerability of Moclobemide + Nicotine Patch | 17 participants |