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Efficacy of Naltrexone in Women's Smoking Cessation

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Andrea King, University of Chicago
ClinicalTrials.gov Identifier:
NCT00271024
First received: December 28, 2005
Last updated: March 13, 2013
Last verified: March 2013
  Purpose

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.

Condition Intervention Phase
Smoking
Smoking Cessation
Drug: Naltrexone (drug)
Drug: Placebo (for Naltrexone)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Naltrexone in Women's Smoking Cessation

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Prolonged Smoking Abstinence: 4 Weeks Post Quit-Date [ Time Frame: 4 Weeks Following Smoking Quit Date (Study week 7) ] [ Designated as safety issue: No ]
    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.

  • Prolonged Smoking Abstinence: 12 Weeks Post Quit-Date [ Time Frame: 12 Weeks Following Smoking Quit Date (Study week 15) ] [ Designated as safety issue: No ]
    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.

  • 7-Day Point Prevalence Smoking Abstinence: 4 Weeks Post Quit-Date [ Time Frame: 4 Weeks Following Smoking Quit Date (Study week 7) ] [ Designated as safety issue: No ]
    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.

  • 7-Day Point Prevalence Smoking Abstinence: 12 Weeks Post Quit-Date [ Time Frame: 12 Weeks Following Smoking Quit Date (Study week 15) ] [ Designated as safety issue: No ]
    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.

  • 7-Day Point Prevalence Smoking Abstinence: 26 Weeks Post Quit-Date [ Time Frame: 26 Weeks Following Smoking Quit Date (Study week 29) ] [ Designated as safety issue: No ]
    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.

  • 7-Day Point Prevalence Smoking Abstinence: 52 Weeks Post Quit-Date [ Time Frame: 52 Weeks Following Smoking Quit Date (Study week 55) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Weight Change at End of Treatment (Smoking Abstinent Only) [ Time Frame: Weight change at 12 weeks post smoking quit date (study week 15) ] [ Designated as safety issue: No ]
    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 End of Treatment (Regardless of Quit Status) [ Time Frame: Weight change at 12 weeks post quit date (study week 15) from smoking quit date ] [ Designated as safety issue: No ]
    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.

  • Opioid Antagonist Reported Side Effects: 1-Week Post Quit Date [ Time Frame: 1-Week Post Quit Date (Study Week 4) ] [ Designated as safety issue: No ]
    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.

  • Opioid Antagonist Reported Side Effects: 4-Weeks Post Quit Date [ Time Frame: 4-Weeks Post Quit Date (Study Week 7) ] [ Designated as safety issue: No ]
    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.


Enrollment: 333
Study Start Date: December 2005
Study Completion Date: March 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Male Naltrexone
50 mg Naltrexone tablet
Drug: Naltrexone (drug)
50 mg q.d. for 13 weeks
Experimental: Female Naltrexone
Females receiving either naltrexone (50 mg)
Drug: Naltrexone (drug)
50 mg q.d. for 13 weeks
Placebo Comparator: Male Placebo
Males receiving Placebo (sugar pill)
Drug: Placebo (for Naltrexone)
Sugar pill manufactured to mimic Naltrexone tablet
Placebo Comparator: Female Placebo
Females receiving placebo (sugar pill)
Drug: Placebo (for Naltrexone)
Sugar pill manufactured to mimic Naltrexone tablet

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00271024

Locations
United States, Illinois
The University of Chicago, Department of Psychiatry
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Andrea C King, PhD The University of Chicago, Department of Psychiatry
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrea King, Associate Professor, University of Chicago
ClinicalTrials.gov Identifier: NCT00271024     History of Changes
Other Study ID Numbers: 13976A (R01 DA016834), R01 DA016834
Study First Received: December 28, 2005
Results First Received: December 19, 2012
Last Updated: March 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Chicago:
Smoking
Smoking Cessation

Additional relevant MeSH terms:
Naltrexone
Central Nervous System Agents
Narcotic Antagonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014