Efficacy of Naltrexone in Women's Smoking Cessation

Study Overview
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Brief Summary
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The purpose of the proposed study is to conduct a randomized, double-blind clinical trial to compare adjunct treatment with 50 mg oral naltrexone vs. placebo in conjunction with standard smoking cessation treatment with nicotine patch and counseling. Hypotheses: Naltrexone will improve smoking cessation quit rates, as measured at the end of active treatment (3 months) and during long term follow up (1 year). Weight and smoking-related variables (i.e., less weight gain, as well as reduced craving and withdrawal) will be important factors by which naltrexone improves smoking cessation outcome. These effects are predicted to be stronger in women compared to men.

Detailed Description
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Although women may be particularly susceptible to the damaging effects of chronic cigarette smoking, evidence indicates that they may have more difficulty in maintaining smoking cessation than men. Given women's reduced response to nicotine replacement and other traditional treatments to habitual cigarette smoking, more targeted pharmacotherapy and intervention strategies may be necessary to improve their quit rates. Preliminary data by our group and others indicate that the opioid antagonist naltrexone may be an effective adjunctive pharmacotherapy approach for female smokers. The purpose of the proposed study is to conduct a randomized clinical trial to compare adjunct treatment with 50 mg oral naltrexone vs. placebo in conjunction with standard smoking cessation treatment with nicotine patch and counseling. Participants (N=324) will be randomized to receive either naltrexone or placebo starting one week prior to the quit date (25 mg for three days; 50 mg thereafter) and continue for 12 weeks after the quit date. The effects of naltrexone will be evaluated during the pre-quit date period, initial smoking cessation, relapse prevention, and at one year follow-up. It is hypothesized that sex will moderate the effects of naltrexone on outcome, with naltrexone improving prolonged abstinence quit rates in women but not in men. The secondary goal will be to elucidate the mechanism underlying women's treatment response to naltrexone. Weight (relative weight gain and weight concerns) and smoking-related variables (reduced cigarette pleasure, taste, craving and relief of negative withdrawal affect) may be important factors by which naltrexone improves quit rates in women. Medication compliance, psychosocial stress and levels of naltrexone's metabolite, 6-B-naltrexol, will also be examined. In sum, the proposed clinical trial will provide a comprehensive study of sex differences in response to adjunct treatment with naltrexone for smoking cessation. Given the public health concerns and significant health consequences of women's continued high rates of smoking, the proposed study may provide important information on a novel treatment strategy targeting the endogenous opioid system to selectively aid in women's smoking cessation.

Official Title
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Efficacy of Naltrexone in Women's Smoking Cessation

Conditions
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Smoking, Smoking Cessation

Intervention / Treatment
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* Drug: Naltrexone (drug)
* Drug: Placebo (for Naltrexone)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65, male or female Cigarette smoker of at least 15 but no more than 40 cigarettes daily for at least two years Current diagnosis of DSM-IV Nicotine Dependence, based on SCID interview Relatively healthy, with no medical or psychiatric conditions that would adversely interact with study parameters (see exclusion criteria for specific details) Desire to quit smoking (self-report rating of interest in quitting at least a 7 on a 10-point scale) Nicometer® cotinine level at baseline at least a 5 on a 6-point scale Reports not quitting smoking in the past three months for more than one week duration Agrees to attend behavioral counseling sessions and complete study measures Has stable residence and telephone and can provide the name of an outside household collateral family member or close friend Exclusion Criteria: Substance Dependence in the last one year (other than DSM-IV Nicotine Dependence) or any history of Opioid Dependence (lifetime) Major psychiatric disorder in the last one year, including Axis I disorders or any history of moderate/severe Axis II Disorder, Bipolar Disorder or Psychotic Disorder, based on SCID interview and standard cut-off thresholds on screening questionnaires Past or current medical disorders (cardiovascular, hepatic, neurological, endocrine, etc.) which may adversely interact with study measures Clinically significant lab test abnormalities, positive urine toxicology, or positive pregnancy test Currently pregnant, plans to become pregnant, or lack of effective birth control over next three months, and/or currently lactating, or plans for breastfeeding over next three months History of adverse reaction to opioid antagonist or nicotine replacement treatment Use of any medication that may adversely interact with study measures (antidepressants, phenothiazines, benzodiazepines, etc.); recent or regular use of an opioid medication Unwillingness to attend smoking cessation treatment sessions, take the nicotine patch, or be randomized into medication or placebo conditions, or be available for follow-up assessments Unwillingness to agree to DNA analysis.

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 |
| --- | --- |
| Experimental: Male Naltrexone<br>50 mg Naltrexone tablet | Drug: Naltrexone (drug)<br>* 50 mg q.d. for 13 weeks<br>|
| Experimental: Female Naltrexone<br>Females receiving either naltrexone (50 mg) | Drug: Naltrexone (drug)<br>* 50 mg q.d. for 13 weeks<br>|
| Placebo Comparator: Male Placebo<br>Males receiving Placebo (sugar pill) | Drug: Placebo (for Naltrexone)<br>* Sugar pill manufactured to mimic Naltrexone tablet<br>|
| Placebo Comparator: Female Placebo<br>Females receiving placebo (sugar pill) | Drug: Placebo (for Naltrexone)<br>* Sugar pill manufactured to mimic Naltrexone tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prolonged Smoking Abstinence: 4 Weeks Post Quit-Date | Prolonged Abstinence at 4 weeks post quit date (Study Week 7). Prolonged Abstinence defined as not smoking (even a puff of a cigarette) at any point during the previous time frame, allowing for a 1-week grace period. | 4 Weeks Following Smoking Quit Date (Study week 7) | 
| Prolonged Smoking Abstinence: 12 Weeks Post Quit-Date | Prolonged Abstinence at 12 weeks post quit date (Study Week 15). Prolonged Abstinence defined as not smoking (even a puff of a cigarette) at any point during the previous time frame, allowing for a 1-week grace period. | 12 Weeks Following Smoking Quit Date (Study week 15) | 
| 7-Day Point Prevalence Smoking Abstinence: 4 Weeks Post Quit-Date | 7-Day Point Prevalence smoking abstinence at 4 weeks post quit date (Study Week 7). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame. | 4 Weeks Following Smoking Quit Date (Study week 7) | 
| 7-Day Point Prevalence Smoking Abstinence: 12 Weeks Post Quit-Date | 7-Day Point Prevalence smoking abstinence at 12 weeks post quit date (Study Week 15). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame. | 12 Weeks Following Smoking Quit Date (Study week 15) | 
| 7-Day Point Prevalence Smoking Abstinence: 26 Weeks Post Quit-Date | 7-Day Point Prevalence smoking abstinence at 29 weeks post quit date (Study Week 29). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame. | 26 Weeks Following Smoking Quit Date (Study week 29) | 
| 7-Day Point Prevalence Smoking Abstinence: 52 Weeks Post Quit-Date | 7-Day Point Prevalence smoking abstinence at 52 weeks post quit date (Study Week 55). 7-Day Point Prevalence abstinence defined as not smoking (even a puff) for seven days in a row or on one day in each of two consecutive weeks during the previous time frame. | 52 Weeks Following Smoking Quit Date (Study week 55) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Change at End of Treatment (Smoking Abstinent Only) | Weight change in lbs at 12 weeks post smoking quit date (study week 15) for only those reporting continued smoking abstinence at the end of treatment. All data are Mean(SEM) and represent positive change, unless otherwise noted. Smoking abstinent for this measure defined as no smoking even 1 puff of a cigarette since the smoking quit date (study week 3), allowing for a 1-week grace period. | Weight change at 12 weeks post smoking quit date (study week 15) | 
| Weight Change at End of Treatment (Regardless of Quit Status) | Weight change at 12 weeks post quit date (study week 15) for the whole sample regardless of quit status. All data is Mean(SEM) and represents a positive change unless otherwise noted. | Weight change at 12 weeks post quit date (study week 15) from smoking quit date | 
| Opioid Antagonist Reported Side Effects: 1-Week Post Quit Date | Participants reporting side effects during the previous week by pill type and sex, 1-week following quit date (Study week 4). Participants rated side effects experienced by None, Mild, or Severe. | 1-Week Post Quit Date (Study Week 4) | 
| Opioid Antagonist Reported Side Effects: 4-Weeks Post Quit Date | Participants reporting side effects during the previous week by pill type and sex, 4-weeks following quit date (Study week 7). Participants rated side effects experienced by None, Mild, or Severe. | 4-Weeks Post Quit Date (Study Week 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Smoking Cessation