Addressing Post Cessation Weight Gain

Study Overview
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Brief Summary
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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
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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.

Official Title
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Varenicline and Lorcaserin for Smoking Cessation and Weight Gain Prevention

Conditions
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Obesity, Smoking Cessation

Intervention / Treatment
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* Drug: lorcaserin
* Drug: Varenicline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be considered for inclusion if they meet all of the following ≥18 years and ≤65 years of age; smoked ≥10 cigarettes/day for the past 6 months; Body Mass Index of 27-39.9 kg/m2; motivated to stop smoking; weight concerned as shown with the Weight Concern Scale; able to participate fully in all aspects of the study; understand and signed the study informed consent. 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: 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.); current moderate or severe depression as assessed by a score of ≥16 on the Center for Epidemiology Studies-Depression; a lifetime history of psychosis, bipolar disorder or schizophrenia; use of anti-psychotic medication within the past 30 days; use of weight-loss medications within the past 30 days or current participation in a program specifically designed to help with weight loss; weight fluctuations of 20 pounds or more in the past 6 months (self-report); use of any treatments for tobacco dependence within the past 30 days; use of an investigational drug within the past 30 days; 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 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); uncontrolled hypertension (systolic >160 mm Hg and/or diastolic >100 mm Hg) documented on 2 separate occasions; current use of medications known to interact with varenicline or lorcaserin. These can include benzodiazepines, narcotics, anti-epileptics; another household member or relative participating in the study; known diabetes; a known allergy to varenicline or lorcaserin. 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. Has an unstable medical condition as determined by the physician investigator 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. Subject currently has cancer [excluding non-melanoma skin cancer] not in remission Known history of seizures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Varenicline plus placebo<br>Subjects will receive open label varenicline (12 weeks) plus a placebo for lorcaserin (24 weeks) | Drug: Varenicline<br>* Chantix is an FDA approved medication for smoking cessation<br>* Other names: Chantix;Drug: Placebo<br>* Placebo for lorcaserin<br>|
| Experimental: Varenicline plus lorcaserin<br>Subjects will receive open label varenicline (12 weeks) plus lorcaserin (24 weeks) | Drug: lorcaserin<br>* lorcaserin is an FDA-approved weight loss medication for overweight and obese patients<br>* Other names: Belviq;Drug: Varenicline<br>* Chantix is an FDA approved medication for smoking cessation<br>* Other names: Chantix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI | BMI change from baseline to week 24 | 24 weeks | 
| Smoking Abstinence | Lorcaserin combined with open label varenicline will be evaluated for improved smoking abstinence compared to placebo | 24 weeks | 
| Waist Circumference | Waist Circumference change from baseline to week 24 | 24 weeks | 
| Fat Mass | Body Fat difference from baseline to week 24. | 24 weeks |