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 women’s but not men’s smoking cessation outcome at the end of active treatment (3 months) and during long term follow up (1 year).
2. Weight and smoking related variables will mediate the relationship between treatment and outcome in female smokers.

Condition	Intervention	Phase
Smoking Smoking Cessation	Drug: Naltrexone (drug)	Phase II

Further study details as provided by University of Chicago:

Primary Outcomes: 1) Point prevalence smoking abstinence at 1, 3, 6, 9, 12 months post quit date.
Secondary Outcomes: 1) Physiological variables (concentration of Naltrexone and 6-B-naltrexol, CO, cotinine); 2) Weight gain and weight concerns; 3) Ratings of cigarette pleasure and taste (positive reinforcement); 4) Ratings of withdrawal affect and craving (negative reinforcement); 5) Psychosocial stress; 6) Medication compliance
Expected Total Enrollment:  324

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.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

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.

Please refer to this study by ClinicalTrials.gov identifier  NCT00271024

Andrea C King, PhD      773-702-6181    aking@yoda.bsd.uchicago.edu
Mihai Raicu, MS      773-702-6188    mraicu@bsd.uchicago.edu

Illinois
      The University of Chicago, Department of Psychiatry, Chicago,  Illinois,  60637,  United States

Study chairs or principal investigators

Andrea C King, PhD,  Principal Investigator,  The University of Chicago, Department of Psychiatry   

Study ID Numbers:  R01 DA016834
Last Updated:  December 28, 2005
Record first received:  December 28, 2005
ClinicalTrials.gov Identifier:  NCT00271024
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-01-10