Clinical trial NCT00271024: Efficacy of Naltrexone in Women's Smoking Cessation
Official title: Efficacy of Naltrexone in Women's Smoking Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smoking
Smoking Cessation
Keywords: Smoking
Smoking Cessation
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2005-12-29
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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:

1. 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).
2. 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.
3. These effects are predicted to be stronger in women compared to men.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-65, male or female
2. Cigarette smoker of at least 15 but no more than 40 cigarettes daily for at least two years
3. Current diagnosis of DSM-IV Nicotine Dependence, based on SCID interview
4. Relatively healthy, with no medical or psychiatric conditions that would adversely interact with study parameters (see exclusion criteria for specific details)
5. Desire to quit smoking (self-report rating of interest in quitting at least a 7 on a 10-point scale)
6. Nicometer® cotinine level at baseline at least a 5 on a 6-point scale
7. Reports not quitting smoking in the past three months for more than one week duration
8. Agrees to attend behavioral counseling sessions and complete study measures
9. Has stable residence and telephone and can provide the name of an outside household collateral family member or close friend

Exclusion Criteria:

1. Substance Dependence in the last one year (other than DSM-IV Nicotine Dependence) or any history of Opioid Dependence (lifetime)
2. 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
3. Past or current medical disorders (cardiovascular, hepatic, neurological, endocrine, etc.) which may adversely interact with study measures
4. Clinically significant lab test abnormalities, positive urine toxicology, or positive pregnancy test
5. 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
6. History of adverse reaction to opioid antagonist or nicotine replacement treatment
7. Use of any medication that may adversely interact with study measures (antidepressants, phenothiazines, benzodiazepines, etc.); recent or regular use of an opioid medication
8. 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
9. Unwillingness to agree to DNA analysis.

Primary outcomes:
measure: Prolonged Smoking Abstinence: 4 Weeks Post Quit-Date
timeFrame: 4 Weeks Following Smoking Quit Date (Study week 7)
measure: Prolonged Smoking Abstinence: 12 Weeks Post Quit-Date
timeFrame: 12 Weeks Following Smoking Quit Date (Study week 15)
measure: 7-Day Point Prevalence Smoking Abstinence: 4 Weeks Post Quit-Date
timeFrame: 4 Weeks Following Smoking Quit Date (Study week 7)
measure: 7-Day Point Prevalence Smoking Abstinence: 12 Weeks Post Quit-Date
timeFrame: 12 Weeks Following Smoking Quit Date (Study week 15)
measure: 7-Day Point Prevalence Smoking Abstinence: 26 Weeks Post Quit-Date
timeFrame: 26 Weeks Following Smoking Quit Date (Study week 29)
measure: 7-Day Point Prevalence Smoking Abstinence: 52 Weeks Post Quit-Date
timeFrame: 52 Weeks Following Smoking Quit Date (Study week 55)
Secondary outcomes:
measure: Weight Change at End of Treatment (Smoking Abstinent Only)
timeFrame: Weight change at 12 weeks post smoking quit date (study week 15)
measure: Weight Change at End of Treatment (Regardless of Quit Status)
timeFrame: Weight change at 12 weeks post quit date (study week 15) from smoking quit date
measure: Opioid Antagonist Reported Side Effects: 1-Week Post Quit Date
timeFrame: 1-Week Post Quit Date (Study Week 4)
measure: Opioid Antagonist Reported Side Effects: 4-Weeks Post Quit Date
timeFrame: 4-Weeks Post Quit Date (Study Week 7)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago, Department of Psychiatry
state: Illinois
Study officials:
affiliation: The University of Chicago, Department of Psychiatry
name: Andrea C King, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: King AC, Meyer PJ. Naltrexone alteration of acute smoking response in nicotine-dependent subjects. Pharmacol Biochem Behav. 2000 Jul;66(3):563-72. doi: 10.1016/s0091-3057(00)00258-6.
citation: King AC. Role of naltrexone in initial smoking cessation: preliminary findings. Alcohol Clin Exp Res. 2002 Dec;26(12):1942-4. doi: 10.1097/01.ALC.0000041003.44118.9B. No abstract available.
citation: Epstein AM, King AC. Naltrexone attenuates acute cigarette smoking behavior. Pharmacol Biochem Behav. 2004 Jan;77(1):29-37. doi: 10.1016/j.pbb.2003.09.017.
citation: King A, de Wit H, Riley RC, Cao D, Niaura R, Hatsukami D. Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Nicotine Tob Res. 2006 Oct;8(5):671-82. doi: 10.1080/14622200600789767.
citation: King AC, Cao D, Zhang L, O'Malley SS. Naltrexone reduction of long-term smoking cessation weight gain in women but not men: a randomized controlled trial. Biol Psychiatry. 2013 May 1;73(9):924-30. doi: 10.1016/j.biopsych.2012.09.025. Epub 2012 Nov 22.