Efficacy of Naltrexone in Women's Smoking Cessation

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00271024

Enrollment

333

Registered

2005-12-29

Start date

2005-12-31

Completion date

2010-03-31

Last updated

2023-03-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Smoking, Smoking Cessation

Keywords

Smoking, Smoking Cessation

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.

Interventions

DRUGNaltrexone (drug)

50 mg q.d. for 13 weeks

DRUGPlacebo (for Naltrexone)

Sugar pill manufactured to mimic Naltrexone tablet

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
7-Day Point Prevalence Smoking Abstinence: 52 Weeks Post Quit-Date	52 Weeks Following Smoking Quit Date (Study week 55)	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.
Prolonged Smoking Abstinence: 12 Weeks Post Quit-Date	12 Weeks Following Smoking Quit Date (Study week 15)	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	4 Weeks Following Smoking Quit Date (Study week 7)	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	12 Weeks Following Smoking Quit Date (Study week 15)	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	26 Weeks Following Smoking Quit Date (Study week 29)	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.
Prolonged Smoking Abstinence: 4 Weeks Post Quit-Date	4 Weeks Following Smoking Quit Date (Study week 7)	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.

Secondary

Measure	Time frame	Description
Weight Change at End of Treatment (Regardless of Quit Status)	Weight change at 12 weeks post quit date (study week 15) from smoking quit date	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	1-Week Post Quit Date (Study Week 4)	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	4-Weeks Post Quit Date (Study Week 7)	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.
Weight Change at End of Treatment (Smoking Abstinent Only)	Weight change at 12 weeks post smoking quit date (study week 15)	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.

Countries

United States

Participant flow

Recruitment details

Enrollment for this study lasted from August 2006-March 2009 with study visits taking place in 3 sites (The University of Chicago, Howard Brown Health Clinic, and the Respiratory Health Association). Follow-up interviews for the study concluded in April 2010.

Pre-assignment details

* N=707 screened for participation (320 met exclusion criteria, 54/387 who passed chose not to participate) * 333 participants were randomized into the trial

Participants by arm

Arm	Count
Naltrexone - MALE Males receiving naltrexone as part of the trial	80
Placebo - MALE Males receiving placebo as part of the trial	77
Naltrexone - FEMALE Females receiving naltrexone as part of the trial	88
Placebo - FEMALE Females receiving placebo as part of the trial	88
Total	333

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Lost Interest	3	4	2	3
Overall Study	Protocol Violation	1	6	5	11
Overall Study	Time Commitment, Scheduling, or Travel	6	2	4	4
Overall Study	Unknown/Unspecified	11	11	8	4
Overall Study	Unpleasant Reaction To Tablet	1	3	4	2

Baseline characteristics

Characteristic	Placebo - MALE	Naltrexone - FEMALE	Naltrexone - MALE	Placebo - FEMALE	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	2 Participants	0 Participants	0 Participants	2 Participants
Age, Categorical Between 18 and 65 years	77 Participants	86 Participants	80 Participants	88 Participants	331 Participants
Age, Continuous	40.21 years STANDARD_DEVIATION 10.98	44.34 years STANDARD_DEVIATION 11.49	38.45 years STANDARD_DEVIATION 10.97	44.95 years STANDARD_DEVIATION 10.45	42.13 years STANDARD_DEVIATION 11.27
Region of Enrollment United States	77 participants	88 participants	80 participants	88 participants	333 participants
Sex: Female, Male Female	0 Participants	88 Participants	0 Participants	88 Participants	176 Participants
Sex: Female, Male Male	77 Participants	0 Participants	80 Participants	0 Participants	157 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	92 / 154	101 / 161
serious Total, serious adverse events	2 / 154	2 / 161

Outcome results

Primary

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.

Time frame: 12 Weeks Following Smoking Quit Date (Study week 15)