Obesity, Smoking Cessation
Conditions
Brief summary
Some individuals smoke with the perception that smoking helps control body weight. Smokers gain an average of as much as 10 pounds in the months following smoking abstinence, with heavier and more-dependent smokers gaining more weight. T The Mayo Clinic Nicotine Research Program will randomize 100 nondiabetic, overweight or obese adult smokers to active lorcaserin or placebo for 24 weeks; all of the subjects will receive open-label varenicline for 12 weeks. The purpose of this study is to assess the efficacy of a 24-week course of lorcaserin for decreasing weight gain after stopping smoking.
Detailed description
This will be a randomized, placebo-controlled, parallel-group clinical trial. Nondiabetic, overweight and obese adult smokers will be randomized to one of three arms: * lorcaserin for 24 weeks in combination with varenicline for 12 weeks; * placebo for 24 weeks in combination with varenicline for 12 weeks; We will assess the following: * changes in weight and Weight Concern * 7-day point-prevalence smoking abstinence weekly through week 24 and prolonged smoking abstinence at 24 and 52 weeks. Subjects will have a target quit date 8 days after starting medication.
Interventions
DRUGlorcaserin
lorcaserin is an FDA-approved weight loss medication for overweight and obese patients
DRUGVarenicline
Chantix is an FDA approved medication for smoking cessation
DRUGPlacebo
Placebo for lorcaserin
Sponsors
National Institute on Drug Abuse (NIDA)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects will be considered for inclusion if they meet all of the following 1. ≥18 years and ≤65 years of age; 2. smoked ≥10 cigarettes/day for the past 6 months; 3. Body Mass Index of 27-39.9 kg/m2; 4. motivated to stop smoking; 5. weight concerned as shown with the Weight Concern Scale; 6. able to participate fully in all aspects of the study; 7. understand and signed the study informed consent. 8. Subject is in good health as determined by the clinical investigators.
Exclusion criteria
Subjects will be ineligible for participation if they have any of the following: 1. current nonspecific suicidal thoughts or a lifetime history of a suicidal attempt (defined by the Columbia-Suicide Severity Rating Scale as a potentially self-injurious act committed with at least some wish to die, as a result of act.); 2. current moderate or severe depression as assessed by a score of ≥16 on the Center for Epidemiology Studies-Depression; 3. a lifetime history of psychosis, bipolar disorder or schizophrenia; 4. use of anti-psychotic medication within the past 30 days; 5. use of weight-loss medications within the past 30 days or current participation in a program specifically designed to help with weight loss; 6. weight fluctuations of 20 pounds or more in the past 6 months (self-report); 7. use of any treatments for tobacco dependence within the past 30 days; 8. use of an investigational drug within the past 30 days; 9. recent history (past 3 months) of abuse of or dependence on a substance other than tobacco. Including: heavy alcohol consumption (If male, drinking \> 4 alcoholic beverages per day for past month and if female, drinking \> 3 alcoholic beverages per day for past month); use of cocaine, heroin, club drugs (i.e., methylenedioxymethamphetamine(MDMA)/ecstasy), methamphetamine, or hallucinogens (e.g., LSD) at any time during the past 3 months; and use of marijuana on a weekly basis for the past 3 months 10. current use of triptans, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRI), selective serotonin-norepinephrine re-uptake inhibitors (SNRI), dextromethorphan, tricyclic antidepressants (TCA), bupropion, lithium, tramadol, tryptophan, and St. John's Wort, or any other medication known to involve the serotonergic neurotransmitter system (see human subjects section); 11. uncontrolled hypertension (systolic \>160 mm Hg and/or diastolic \>100 mm Hg) documented on 2 separate occasions; 12. current use of medications known to interact with varenicline or lorcaserin. These can include benzodiazepines, narcotics, anti-epileptics; 13. another household member or relative participating in the study; 14. known diabetes; 15. a known allergy to varenicline or lorcaserin. 16. Women who are pregnant or lactating, or who are of childbearing potential and are likely to become pregnant during the medication phase but are not willing to use a reliable form of contraception, will also be excluded. Reliable forms of contraception include oral contraception, diaphragm or condom (with spermicide), injections, intrauterine device, surgical sterilization, and abstinence. 17. Has an unstable medical condition as determined by the physician investigator 18. Subject describes having a medical history of: a) unstable angina; b) myocardial infarction within the past 3 months; c) coronary angioplasty or d) an untreated cardiac dysrhythmia. 19. Subject currently has cancer \[excluding non-melanoma skin cancer\] not in remission 20. Known history of seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post Cessation Weight Gain (kg) | 24 weeks | weight (kg) change from baseline to week 24 among subjects who meet criteria for prolonged smoking abstinence at week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMI | 24 weeks | BMI change from baseline to week 24 |
| Smoking Abstinence | 24 weeks | Lorcaserin combined with open label varenicline will be evaluated for improved smoking abstinence compared to placebo |
| Waist Circumference | 24 weeks | Waist Circumference change from baseline to week 24 |
| Fat Mass | 24 weeks | Body Fat difference from baseline to week 24. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place between June 16th, 2016 to January 22nd, 2020. Recruitment was in three phases: initial phone pre-screen, followed by a consent visit and study screen, and finally a randomization visit. All visits took place at a medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Plus Placebo Subjects will receive open label varenicline (12 weeks) plus a placebo for lorcaserin (24 weeks)
Varenicline: Chantix is an FDA approved medication for smoking cessation
Placebo: Placebo for lorcaserin | 44 |
| Varenicline Plus Lorcaserin Subjects will receive open label varenicline (12 weeks) plus lorcaserin (24 weeks)
lorcaserin: lorcaserin is an FDA-approved weight loss medication for overweight and obese patients
Varenicline: Chantix is an FDA approved medication for smoking cessation | 40 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Early stop by FDA | 5 | 2 |
| Overall Study | Lost to Follow-up | 5 | 9 |
| Overall Study | Unspecified reason | 6 | 8 |
| Overall Study | Withdrawal by Subject | 9 | 3 |
Baseline characteristics
| Characteristic | Varenicline Plus Lorcaserin | Varenicline Plus Placebo | Total |
|---|---|---|---|
| Age, Continuous | 43.4 years STANDARD_DEVIATION 10.98 | 41.3 years STANDARD_DEVIATION 9.05 | 42.3 years STANDARD_DEVIATION 10.01 |
| Baseline Cigarettes per day | 17.9 cigarettes per day STANDARD_DEVIATION 5.96 | 17.2 cigarettes per day STANDARD_DEVIATION 5.59 | 17.5 cigarettes per day STANDARD_DEVIATION 5.75 |
| Baseline Weight | 93.4 kg STANDARD_DEVIATION 14.7 | 91.8 kg STANDARD_DEVIATION 15.46 | 92.6 kg STANDARD_DEVIATION 15.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 42 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 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 | 37 Participants | 41 Participants | 78 Participants |
| Sex: Female, Male Female | 25 Participants | 30 Participants | 55 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 40 |
| other Total, other adverse events | 21 / 44 | 18 / 40 |
| serious Total, serious adverse events | 0 / 44 | 0 / 40 |
Outcome results
Primary
Post Cessation Weight Gain (kg)
weight (kg) change from baseline to week 24 among subjects who meet criteria for prolonged smoking abstinence at week 24
Time frame: 24 weeks
Population: Restricted to those who met criteria for prolonged abstinence at week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Plus Placebo | Post Cessation Weight Gain (kg) | 0.7 kg | Standard Deviation 8.38 |
| Varenicline Plus Lorcaserin | Post Cessation Weight Gain (kg) | 2.2 kg | Standard Deviation 2.07 |
Secondary
BMI
BMI change from baseline to week 24
Time frame: 24 weeks
Population: Restricted to those who met criteria for prolonged abstinence at week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Plus Placebo | BMI | 0.5 kg/m^2 | Standard Deviation 2.91 |
| Varenicline Plus Lorcaserin | BMI | 0.8 kg/m^2 | Standard Deviation 0.72 |
Secondary
Fat Mass
Body Fat difference from baseline to week 24.
Time frame: 24 weeks
Population: Restricted to those who met criteria for prolonged abstinence at week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Plus Placebo | Fat Mass | 0.4 kg | Standard Deviation 7.12 |
| Varenicline Plus Lorcaserin | Fat Mass | 2.2 kg | Standard Deviation 2.74 |
Secondary
Smoking Abstinence
Lorcaserin combined with open label varenicline will be evaluated for improved smoking abstinence compared to placebo
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Plus Placebo | Smoking Abstinence | 13 Participants |
| Varenicline Plus Lorcaserin | Smoking Abstinence | 8 Participants |
Secondary
Waist Circumference
Waist Circumference change from baseline to week 24
Time frame: 24 weeks
Population: Restricted to those who met criteria for prolonged abstinence at week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline Plus Placebo | Waist Circumference | 0.8 cm | Standard Deviation 7.6 |
| Varenicline Plus Lorcaserin | Waist Circumference | -0.1 cm | Standard Deviation 2.97 |