Addressing Post Cessation Weight Gain

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02412631
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 84
• Location: 1
• Arms: 2
• Actual Duration (Months): 46.1
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Smoking Cessation	Drug: lorcaserin; Drug: Varenicline; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Varenicline and Lorcaserin for Smoking Cessation and Weight Gain Prevention
• Actual Study Start Date: Jun 15, 2016
• Actual Primary Completion Date: Apr 17, 2020
• Actual Study Completion Date: Apr 17, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. BMI [24 weeks]

   BMI change from baseline to week 24

2. Smoking Abstinence [24 weeks]

   Lorcaserin combined with open label varenicline will be evaluated for improved smoking abstinence compared to placebo

3. Waist Circumference [24 weeks]

   Waist Circumference change from baseline to week 24

4. Fat Mass [24 weeks]

   Body Fat difference from baseline to week 24.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Ryan T Hurt, MD, PhD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 10, 2018

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Ryan T. Hurt, M.D., Ph.D., Associate Professor, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02412631
• Other Study ID Numbers: 15-005230; 1K23DA037299-01A1; 14-005682
• First Posted: Apr 9, 2015
• Last Update Posted: Jun 10, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Weight Gain; Varenicline

Study Results

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.

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	44	40
COMPLETED	18	16
NOT COMPLETED	26	24

Baseline Characteristics

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	44	40	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.3 (9.05)	43.4 (10.98)	42.3 (10.01)
Sex: Female, Male (Count of Participants)
Female	30 68.2%	25 62.5%	55 65.5%
Male	14 31.8%	15 37.5%	29 34.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.5%	0 0%	2 2.4%
Not Hispanic or Latino	42 95.5%	40 100%	82 97.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 5%	2 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	41 93.2%	37 92.5%	78 92.9%
More than one race	3 6.8%	1 2.5%	4 4.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Baseline Cigarettes per day (cigarettes per day) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes per day]	17.2 (5.59)	17.9 (5.96)	17.5 (5.75)
Baseline Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	91.8 (15.46)	93.4 (14.7)	92.6 (15.03)

Outcome Measures

1. Primary Outcome

Title	Post Cessation Weight Gain (kg)
Description	weight (kg) change from baseline to week 24 among subjects who meet criteria for prolonged smoking abstinence at week 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Restricted to those who met criteria for prolonged abstinence at week 24.

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin
Arm/Group Description	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	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
Measure Participants	13	8
Mean (Standard Deviation) [kg]	0.7 (8.38)	2.2 (2.07)

2. Secondary Outcome

Title	BMI
Description	BMI change from baseline to week 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Restricted to those who met criteria for prolonged abstinence at week 24.

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin
Arm/Group Description	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	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
Measure Participants	13	8
Mean (Standard Deviation) [kg/m^2]	0.5 (2.91)	0.8 (0.72)

3. Secondary Outcome

Title	Smoking Abstinence
Description	Lorcaserin combined with open label varenicline will be evaluated for improved smoking abstinence compared to placebo
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin
Arm/Group Description	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	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
Measure Participants	44	40
Count of Participants [Participants]	13 29.5%	8 20%

4. Secondary Outcome

Title	Waist Circumference
Description	Waist Circumference change from baseline to week 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Restricted to those who met criteria for prolonged abstinence at week 24.

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin
Arm/Group Description	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	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
Measure Participants	13	8
Mean (Standard Deviation) [cm]	0.8 (7.60)	-0.1 (2.97)

5. Secondary Outcome

Title	Fat Mass
Description	Body Fat difference from baseline to week 24.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Restricted to those who met criteria for prolonged abstinence at week 24.

Arm/Group Title	Varenicline Plus Placebo	Varenicline Plus Lorcaserin
Arm/Group Description	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	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
Measure Participants	13	8
Mean (Standard Deviation) [kg]	0.4 (7.12)	2.2 (2.74)

Adverse Events

Time Frame	Adverse events (AE) were collected throughout the 24 week study period.
Adverse Event Reporting Description	Reported AEs were included in this section.
Arm/Group Title	Varenicline Plus Placebo		Varenicline Plus Lorcaserin
Arm/Group Description	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		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
All Cause Mortality
	Varenicline Plus Placebo		Varenicline Plus Lorcaserin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/40 (0%)
Serious Adverse Events
	Varenicline Plus Placebo		Varenicline Plus Lorcaserin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Varenicline Plus Placebo		Varenicline Plus Lorcaserin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/44 (47.7%)		18/40 (45%)
Gastrointestinal disorders
Constipation	3/44 (6.8%)		5/40 (12.5%)
GI	5/44 (11.4%)		4/40 (10%)
Nausea	8/44 (18.2%)		5/40 (12.5%)
General disorders
Fatigue	2/44 (4.5%)		5/40 (12.5%)
Sleep disorders	9/44 (20.5%)		7/40 (17.5%)
Dry Mouth	0/44 (0%)		1/40 (2.5%)
Nervous system disorders
Headache	4/44 (9.1%)		2/40 (5%)
Mood	0/44 (0%)		3/40 (7.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.