Nicotine Dependence
Conditions
Keywords
Tobacco, Smoking, Weight, Weight perception, Naltrexone
Brief summary
Weight gain after quitting smoking is an important barrier to treatment for many smokers. This study will test a drug called naltrexone with weight-concerned smokers to investigate whether or not this drug both improves smoking cessation quit rates and minimizes post quit weight gain.
Detailed description
This is a 6-month randomized, double-blind, placebo controlled trial of 25 mg naltrexone for smoking cessation in a sample of 270 male and female weight-concerned smokers. Participants also receive transdermal nicotine replacement therapy during the first 8 weeks of the study, which they begin on their quit date. Naltrexone study medication will be started a week before their quit date and continued through the six-month period. Brief behavioral counseling and research assessments are provided for two sessions prior to the quit date and then weekly for two weeks, bi-weekly for a month and every four weeks thereafter. A follow-up appointment is completed at 12 months after participants' quit date. The primary outcomes are six-month point prevalence abstinence and post-cessation weight gain for those who are continuously abstinent (not even a puff). Secondary outcomes include an examination of alcohol consumption, evaluation of urges, other measures of smoking cessation success, point prevalence abstinence at 12 months, and food preferences. A number of tertiary measures will be obtained for examining predictors of smoking cessation, weight gain, and naltrexone response.
Interventions
DRUGNaltrexone
Drug: Naltrexone 12.5 mg oral capsule once per day for 1 day then 25 mg oral capsule once per day for 27 weeks
DRUGTransdermal nicotine replacement
Transdermal nicotine replacement (21 mg for first 6 weeks post-quit then 14 mg for 2 weeks) once per day + naltrexone 25 mg oral capsule once per day
BEHAVIORALBehavioral counseling
Brief behavioral counseling and research assessments are provided for two sessions prior to the quit date and then weekly for two weeks, bi-weekly for a month and every four weeks thereafter.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Concern about gaining weight after quitting. This will be assessed using questionnaires that will provide a rating system to determine qualified participants. * 2\. Age 18 and older. * 3\. Willingness and ability to give written consent. * 4\. Smoking greater than 10 cigarettes per day for at least 1 year. * 5\. At least one prior attempt to stop smoking. * 6\. Baseline expired carbon-monoxide level of at least 10 ppm. * 7\. Weigh at least 100 lbs. * 8\. English speaking. * 9\. One person per household.
Exclusion criteria
* 1\. Pregnant or nursing women or women attempting to conceive. * 2\. Unstable cardiac disease. * 3\. History of dermatoses. * 4\. Current alcohol or drug dependence other than nicotine dependence. * 5\. Serious current neurologic, psychiatric or medical illness, including those with a significant risk of committing suicide based on history or investigator's judgment. * 6\. Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid antagonist, will make these medications ineffective). * 7\. History of cirrhosis or significant hepatocellular injury as evidenced by SGOT or SGPT \>3 x normal or elevated bilirubin. * 8\. Current use of smokeless tobacco, pipes, cigars, nicotine gum, patch, nasal spray, inhaler, or lozenges. * 9\. Patients requiring concomitant therapy with any psychotropic drug or on any drug with a psychotropic component except those who are on a stable dose of an Selective Serotonin Reuptake Inhibitor for at least two months for the indications of Major Depressive Disorder, Premenstrual Syndrome (PMS) or Premenstrual Dysphoric Disorder (PMDD). * 10\. Subjects with a positive opiate urine drug screen will be excluded to avoid precipitating opiate withdrawal. * 11\. Current use of opiates. * 12\. Currently on a medically prescribed diet.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight Gain at 26 Weeks. | 26 weeks | Weight change from baseline measured at 26 weeks. |
| Point Prevalence Smoking Abstinence at 26 Weeks. | 26 weeks | The number of people that were abstinent from cigarette smoking at 26 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight Gain at 6 Weeks. | 6 weeks | Weight change from baseline measured at 6 weeks. |
| Point Prevalence Smoking Abstinence at 6 Weeks | 6 weeks | The number of people that were abstinent from cigarette smoking at 6 weeks. |
| Cigarettes Smoked Per Day. | 26 weeks | Average number of cigarettes smoked per day at 26 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone Arm 1 (Experimental) = Transdermal nicotine replacement (21 mg for first 6 weeks post-quit then 14 mg for 2 weeks) once per day + Naltrexone 25 mg oral capsule once per day
Transdermal nicotine replacement : Transdermal nicotine replacement (21 mg for first 6 weeks post-quit then 14 mg for 2 weeks) once per day + naltrexone 25 mg oral capsule once per day
Naltrexone : Drug: Naltrexone 12.5 mg oral capsule once per day for 1 day then 25 mg oral capsule once per day for 27 weeks
Behavioral counseling : Brief behavioral counseling and research assessments are provided for two sessions prior to the quit date and then weekly for two weeks, bi-weekly for a month and every four weeks thereafter. | 87 |
| Placebo Arm 2 (Placebo Comparator) = Transdermal nicotine replacement (21 mg for first 6 weeks post-quit then 14 mg for 2 weeks) once per day + Placebo Naltrexone 25 mg oral capsule once per day
Behavioral counseling : Brief behavioral counseling and research assessments are provided for two sessions prior to the quit date and then weekly for two weeks, bi-weekly for a month and every four weeks thereafter. | 85 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost Interest | 29 | 32 |
| Overall Study | Lost to Follow-up | 26 | 17 |
| Overall Study | Scheduling Conflict | 2 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
| Overall Study | Withdrawn by PI | 1 | 1 |
Baseline characteristics
| Characteristic | Naltrexone | Placebo | Total |
|---|---|---|---|
| Age Continuous | 43.2 years STANDARD_DEVIATION 10 | 45.5 years STANDARD_DEVIATION 11.3 | 44.4 years STANDARD_DEVIATION 10.7 |
| Sex: Female, Male Female | 62 Participants | 61 Participants | 123 Participants |
| Sex: Female, Male Male | 25 Participants | 24 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 87 | 51 / 85 |
| serious Total, serious adverse events | 2 / 87 | 2 / 85 |
Outcome results
Primary
Point Prevalence Smoking Abstinence at 26 Weeks.
The number of people that were abstinent from cigarette smoking at 26 weeks.
Time frame: 26 weeks
Population: All patients who were randomized comprised the primary ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naltrexone | Point Prevalence Smoking Abstinence at 26 Weeks. | 19 participants |
| Placebo | Point Prevalence Smoking Abstinence at 26 Weeks. | 23 participants |
Primary
Weight Gain at 26 Weeks.
Weight change from baseline measured at 26 weeks.
Time frame: 26 weeks
Population: All patients who were randomized comprised the primary ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone | Weight Gain at 26 Weeks. | 6.75 pounds | Standard Deviation 8.94 |
| Placebo | Weight Gain at 26 Weeks. | 9.71 pounds | Standard Deviation 9.19 |
Secondary
Cigarettes Smoked Per Day.
Average number of cigarettes smoked per day at 26 weeks.
Time frame: 26 weeks
Population: Patients were analyzed per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone | Cigarettes Smoked Per Day. | 7.10 number of cigarettes | Standard Deviation 8.43 |
| Placebo | Cigarettes Smoked Per Day. | 7.85 number of cigarettes | Standard Deviation 8.35 |
Secondary
Point Prevalence Smoking Abstinence at 6 Weeks
The number of people that were abstinent from cigarette smoking at 6 weeks.
Time frame: 6 weeks
Population: All patients who were randomized comprised the primary ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naltrexone | Point Prevalence Smoking Abstinence at 6 Weeks | 33 participants |
| Placebo | Point Prevalence Smoking Abstinence at 6 Weeks | 43 participants |
Secondary
Weight Gain at 6 Weeks.
Weight change from baseline measured at 6 weeks.
Time frame: 6 weeks
Population: All patients who were randomized comprised the primary ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone | Weight Gain at 6 Weeks. | 2.53 pounds | Standard Deviation 4.58 |
| Placebo | Weight Gain at 6 Weeks. | 2.19 pounds | Standard Deviation 4.2 |