Nicotine Dependence
Conditions
Keywords
Nicotine addiction, Cigarette smoking, Smoking cessation, lorcaserin, Belviq, Nicotine patches
Brief summary
This study plans to compare the efficacy of the nicotine patch / lorcaserin combination treatment vs. the nicotine patch alone in terms of leading to a reduction in smoking behavior and withdrawal symptoms.
Detailed description
This study proposes to investigate the potential efficacy of a combination of two FDA-approved agents, nicotine patch and lorcaserin, for smoking cessation treatment. The nicotine patch which provides a sustained low dose of nicotine is a nicotine receptor agonist. Lorcaserin, a serotonin 5-hydroxytryptamine receptor 2C (5-HT2C) agonist, is a drug that is FDA-approved for weight loss, and has also recently been shown to be efficacious for smoking cessation. Given that these drugs act through distinct mechanisms it is hoped that the combination will prove more efficacious than either drug alone. It is also hypothesized that the combination will reduce weight gain commonly seen after smoking cessation.
Interventions
DRUGlorcaserin
DRUGnicotine patch
DRUGplacebo lorcaserin
Sponsors
National Institute on Drug Abuse (NIDA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18-65 years old; * Smoke an average of at least 10 cigarettes per day; * Have smoked at least one cumulative year; * Have an expired air CO reading of at least 10ppm; * Body weight of \>50 kg (110 lbs.) * Able to read and understand English; * Express a desire to quit smoking in the next thirty days.
Exclusion criteria
* 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, diagnosed by coronary angiogram; * Lifetime history of heart attack; * Cardiac rhythm disorder (irregular heart rhythm); * Chest pain in the last month (unless history, exam, and ECG clearly indicate a non-cardiac source); * Symptomatic cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure); * Diagnosis of liver disease or kidney disorder (except kidney stones, gallstones); * Gastrointestinal problems (e.g. Celiac disease, Crohn's dx Ulcerative Colitis) 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, and seizure disorder); * 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 and screening 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); * HIV, Hepatitis B, or Hepatitis C * History of tuberculosis or recent positive purified protein derivative (PPD) test * Other major medical condition; * Current psychiatric disease (with the exception of anxiety disorders, obsessive compulsive disorder (OCD) and ADHD); * Suicidal ideating (thinking about ways to commit suicide) (within the past 10 years) or lifetime occurrence of attempted suicide; * Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 (Thoughts that you would be better off dead, or of hurting yourself in some way) will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment; * Bulimia or anorexia; * BMI of \< 18.5 kg/m2; * Prior use of fenfluramine or dexfenfluramine * 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), Unless recent use of prescription Opiates, Benzodiazepines for management of acute symptoms. * Experimental (investigational) drugs; * Psychiatric medications including antidepressants (selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), St. John's Wort), lithium, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Phentermine, triptans, tryptophan, linezolid, dextromethorphan, opiates, tramadol, or dopamine agonists; * Any agents that have documented correlation with increased incidence of valvulopathy and/or pulmonary hypertension (e.g., cyproheptadine, trazodone, nefazodone, amoxapine, tricyclic antidepressants, mirtazapine, pergolide, ergotamine, methysergide) (or anticipated use during the study); * Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes; * Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine patch, nicotine replacement therapy or any other smoking cessation aid. * Concurrent use of a serotonergic agent/combination associated with severe serotonin syndrome (within the past 30 days); * Use of cigar, cigarillos, pipe, Hookah, dissolvable nicotine, snuff, chewing tobacco more than once per month. * Use of e-cigarettes once per month or more. * Self-report of consuming 4 or more alcoholic drinks on 1 or more days per week; * Significant adverse reaction to lorcaserin or nicotine patch in the past. * Current participation or recent participation (in the past 30 days) in another smoking study at the investigators Center or another research facility. * Current participation in another research study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-lapse | Week 2 pre quit day | Two weeks after treatment is initiated, with nicotine patch + lorcaserin or nicotine patch alone, but still two weeks prior to the quit day, subjects will be evaluated in a modified version of the McKee Smoking Lapse Task. In this task smokers, who have been abstinent for 2 hours will be provided with the option to smoke at any time, but paid by the minute for remaining abstinent with progressively decreasing payments over an hour. |
| Smoking Withdrawal | Week 2 pre quit day | At the study visit above (two week post treatment initiation but 2 weeks prior to quit day), withdrawal symptoms will be assessed after 2 hours of smoking abstinence using the Shiffman-Jarvik (short form) questionnaire, which consists of 9 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 9 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, and Arousal. The range of scores for each subscale will be 1-7, with higher scores indicating more of the withdrawal symptom having been experienced. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight Gain Following Continuous Four-week Abstinence From Smoking | Week 10 post quit day | Among smoking-abstinent participants, weight gain relative to baseline will be assessed. |
| Number of Participants Reporting 6-month Smoking Abstinence | 6 months post Quit Day | Number of participants who reported not smoking for the previous seven days when called for 6-month follow-up, confirmed by expired air carbon monoxide (CO). |
| Number of Participants Reporting Smoking Abstinence | Weeks 7-10 post quit day | Number of participants who reported continuous four-week abstinence from smoking (weeks 7-10 post target quit date), confirmed by expired air carbon monoxide (CO). |
| Adherence to Lorcaserin + Nicotine Patch Treatment as Indicator of Tolerability | Two Weeks pre and 10 weeks post quit day | Tolerability of the lorcaserin + nicotine patch treatment will be assessed by calculating adherence scores based on the percentage of days on which the study drugs were taken between visits as reported by participants on diaries. |
| Percentage of Change in Ad Libitum Smoking at End of Week 2 | Week 2 pre quit day | To evaluate the effects of lorcaserin on ad libitum (ad lib) smoking, the percent change in reported number of cigarettes smoked from baseline to the end of week 2 (the day prior to the 2nd study visit) will be calculated. |
| Number of Participants Reporting Tolerability Issues With Lorcaserin + Nicotine Patch Treatment | Two Weeks pre and 10 weeks post quit day | Tolerability of the lorcaserin + nicotine patch treatment will be assessed by tabulating the number of participants rating side effects \> moderate. |
Countries
United States
Participant flow
Recruitment details
Recruitment began on 11/8/2016 and ended on 2/20/2018. Of the 97 subjects (subjs.) consented during this period, 61 subjects met all study criteria, attended the first study visit, were randomized and received study intervention.
Pre-assignment details
Of the 97 subjs. enrolled, 36 were withdrawn by study staff or withdrew voluntarily from further participation prior to the 1st study visit (V1): 14 did not meet inclusion criteria, 16 met exclusion criteria, 3 were unable to meet study requirements, 2 were excluded due to laboratory values, and 1 was excluded by the medical staff.
Participants by arm
| Arm | Count |
|---|---|
| Lorcaserin + Patch Participants will receive lorcaserin (10mg twice a day) and nicotine patches (21mg/24hr) for 14 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.
lorcaserin
nicotine patch | 31 |
| Patch Participants will receive nicotine patches (21mg/24hr) and placebo lorcaserin for 2 weeks; after 2 weeks participants will begin to receive active lorcaserin (10mg twice a day) along with the nicotine patches for 12 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.
lorcaserin
nicotine patch
placebo lorcaserin | 30 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First 2 Weeks | Physician Decision | 1 | 1 |
| First 2 Weeks | Withdrawal by Subject | 0 | 2 |
| Weeks 3 to 14 | Lost to Follow-up | 3 | 4 |
| Weeks 3 to 14 | Withdrawal by Subject | 13 | 7 |
Baseline characteristics
| Characteristic | Lorcaserin + Patch | Total | Patch |
|---|---|---|---|
| Age, Continuous | 47 years | 49 years | 50 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 20 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 40 Participants | 21 Participants |
| Region of Enrollment United States | 31 Participants | 61 Participants | 30 Participants |
| Sex: Female, Male Female | 24 Participants | 46 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 27 |
| other Total, other adverse events | 35 / 56 | 12 / 27 |
| serious Total, serious adverse events | 0 / 56 | 1 / 27 |
Outcome results
Primary
Smoking Withdrawal
At the study visit above (two week post treatment initiation but 2 weeks prior to quit day), withdrawal symptoms will be assessed after 2 hours of smoking abstinence using the Shiffman-Jarvik (short form) questionnaire, which consists of 9 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 9 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, and Arousal. 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: Week 2 pre quit day
Population: Four participants dropped out of the study, 3 more reported having already quit smoking before the Smoking Lapse Task occurred, and 1 did not complete the withdrawal questionnaire; therefore, we have lapse data for only 53 participants rather than 61.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lorcaserin + Patch | Smoking Withdrawal | Craving | 2.81 score on a scale | Standard Deviation 1.271 |
| Lorcaserin + Patch | Smoking Withdrawal | Negative Affect | 2.15 score on a scale | Standard Deviation 0.788 |
| Lorcaserin + Patch | Smoking Withdrawal | Arousal | 4.73 score on a scale | Standard Deviation 1.014 |
| Lorcaserin + Patch | Smoking Withdrawal | Appetite | 3.11 score on a scale | Standard Deviation 1.685 |
| Patch | Smoking Withdrawal | Appetite | 2.80 score on a scale | Standard Deviation 1.607 |
| Patch | Smoking Withdrawal | Craving | 2.91 score on a scale | Standard Deviation 1.219 |
| Patch | Smoking Withdrawal | Arousal | 4.72 score on a scale | Standard Deviation 1.251 |
| Patch | Smoking Withdrawal | Negative Affect | 2.21 score on a scale | Standard Deviation 0.937 |
Primary
Time-to-lapse
Two weeks after treatment is initiated, with nicotine patch + lorcaserin or nicotine patch alone, but still two weeks prior to the quit day, subjects will be evaluated in a modified version of the McKee Smoking Lapse Task. In this task smokers, who have been abstinent for 2 hours will be provided with the option to smoke at any time, but paid by the minute for remaining abstinent with progressively decreasing payments over an hour.
Time frame: Week 2 pre quit day
Population: Four participants dropped out of the study and 3 more reported having already quit smoking before the Smoking Lapse Task occurred; therefore, we have lapse data for only 54 participants rather than 61.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lorcaserin + Patch | Time-to-lapse | 51.97 Minutes | Standard Deviation 18.331 |
| Patch | Time-to-lapse | 56.44 Minutes | Standard Deviation 12.49 |
Secondary
Adherence to Lorcaserin + Nicotine Patch Treatment as Indicator of Tolerability
Tolerability of the lorcaserin + nicotine patch treatment will be assessed by calculating adherence scores based on the percentage of days on which the study drugs were taken between visits as reported by participants on diaries.
Time frame: Two Weeks pre and 10 weeks post quit day
Population: Two weeks pre-quit day, all study subjects were switched to taking active lorcaserin for the duration of the study. Fourteen subjects either dropped out prior to Visit 3 (the first visit after all subjects were on combined treatment) or had missing or incomplete diaries, so data are only available for 47 subjects during this phase of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lorcaserin + Patch | Adherence to Lorcaserin + Nicotine Patch Treatment as Indicator of Tolerability | 72.15 percentage of days using study drugs | Standard Deviation 0.339 |
Secondary
Number of Participants Reporting 6-month Smoking Abstinence
Number of participants who reported not smoking for the previous seven days when called for 6-month follow-up, confirmed by expired air carbon monoxide (CO).
Time frame: 6 months post Quit Day
Population: Two weeks pre-quit day, all study subjects were switched to taking active lorcaserin for the duration of the study. Nine participants reported continuous 7-day abstinence from smoking 6 months post quit-day, confirmed by expired air carbon monoxide (CO).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lorcaserin + Patch | Number of Participants Reporting 6-month Smoking Abstinence | 9 Participants |
Secondary
Number of Participants Reporting Smoking Abstinence
Number of participants who reported continuous four-week abstinence from smoking (weeks 7-10 post target quit date), confirmed by expired air carbon monoxide (CO).
Time frame: Weeks 7-10 post quit day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lorcaserin + Patch | Number of Participants Reporting Smoking Abstinence | 9 Participants |
| Patch | Number of Participants Reporting Smoking Abstinence | 10 Participants |
Secondary
Number of Participants Reporting Tolerability Issues With Lorcaserin + Nicotine Patch Treatment
Tolerability of the lorcaserin + nicotine patch treatment will be assessed by tabulating the number of participants rating side effects \> moderate.
Time frame: Two Weeks pre and 10 weeks post quit day
Population: Two weeks pre-quit day, all study subjects were switched to taking active lorcaserin for the duration of the study. Twelve participants dropped out of the study prior to the next study visit, therefore side effects data from 2 weeks pre-quit to the end of the study are only available for 49 participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lorcaserin + Patch | Number of Participants Reporting Tolerability Issues With Lorcaserin + Nicotine Patch Treatment | 26 Participants |
Secondary
Percentage of Change in Ad Libitum Smoking at End of Week 2
To evaluate the effects of lorcaserin on ad libitum (ad lib) smoking, the percent change in reported number of cigarettes smoked from baseline to the end of week 2 (the day prior to the 2nd study visit) will be calculated.
Time frame: Week 2 pre quit day
Population: There are insufficient data for 9 participants in the Lorcaserin + Patch group and for 8 participants in the Patch only group (due to participant dropout or incomplete or unreturned diaries) so this analysis excluded those individuals.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lorcaserin + Patch | Percentage of Change in Ad Libitum Smoking at End of Week 2 | -35.58 percentage of change | Standard Deviation 0.396 |
| Patch | Percentage of Change in Ad Libitum Smoking at End of Week 2 | -47.13 percentage of change | Standard Deviation 0.482 |
Secondary
Weight Gain Following Continuous Four-week Abstinence From Smoking
Among smoking-abstinent participants, weight gain relative to baseline will be assessed.
Time frame: Week 10 post quit day
Population: Two weeks pre-quit day, all study subjects were switched to taking active lorcaserin for the duration of the study. Nineteen participants reported continuous four-week abstinence from smoking (weeks 7-10 post target quit date), confirmed by expired air carbon monoxide (CO).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lorcaserin + Patch | Weight Gain Following Continuous Four-week Abstinence From Smoking | -0.35 weight gain (in lbs) | Standard Deviation 7.203 |