Effectiveness of GW468816, an NMDA Glycine Site Antagonist, for Prevention of Relapse to Smoking
The purpose of this study is to evaluate the efficacy of the glycine antagonist, GW468816, compared with placebo on duration of abstinence and rates of relapse in recently quit female smokers in a randomized, double-blind, five-week clinical trial.
According to the investigators, the new medication, GW468816, is thought to send certain signals in the brain that may be effective in helping people stay abstinent after they have recently quit smoking. GW468816 is a non-nicotine drug.
The investigators of this study hypothesize that subjects receiving GW468816 will demonstrate a significantly longer time to relapse to smoking than those in the placebo group, as measured by the primary outcome measure (see below).
Drug: Placebo Comparator: Placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Double-Blind, Placebo-Controlled Trial of the NMDA Glycine Site Antagonist, GW468816, for Prevention of Relapse to Smoking|
- Time to Relapse to Smoking in the 5-week Relapse Prevention Phase. [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
- Number of Abstinent and Nonabstinent Participants at End of 5 Week Placebo-controlled Relapse Prevention Trial [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]
- Days to Relapse Within the 60 Days Following Randomization [ Time Frame: 60 days ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||June 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
Glycine Antagonist GW468816, 200 mg/day, for a 5-week trial
Pharmacotherapies for Relapse Prevention
Other Name: GW468816: NMDA glycine-site antagonist
Placebo Comparator: Placebo
Placebo, 200 mg/day, for a 5-week trial
|Drug: Placebo Comparator: Placebo|
Smoking is the leading cause of preventable mortality in developed countries. Pharmacotherapy, including bupropion and nicotine replacement therapy (NRT), is universally recommended for smoking cessation treatment; however, even with treatment, the majority of smokers either fail to quit in the short term or relapse in the first year. The high failure rate reported for smoking cessation, then, presents a challenge to explore innovative approaches to treating relapse to smoking.
The purpose of this study, then, is to evaluate the efficacy of the glycine antagonist, GW468816, compared with placebo on duration of abstinence and rates of relapse in female outpatient smokers during a randomized, double-blind, five-week clinical trial.
To do this, the investigators will conduct a two-phase study, in which 300 adult, female outpatient smokers will be enrolled.
Phase I will consist of an 8-week smoking cessation study in which nicotine replacement therapy (NRT) and a behavioral intervention are openly administered on a tapered schedule. Participants who are able to quit smoking after 7 weeks in this preliminary study will then be eligible to enter Phase II.
Phase II is a 5-week, double-blind, placebo-controlled, relapse prevention trial with the investigational medication, GW468816.
Participants in the Phase I smoking cessation study will begin by receiving nicotine replacement therapy in the form of the patch and brief support to stop smoking. Participants will be required to schedule office visits every 1-2 weeks throughout Phase I.
Subjects who are abstinent at the end of Phase I will be eligible to continue Phase II, in which they will be randomly assigned by chance to receive the investigational medication, GW468816, at 200 mg or placebo (a pill that looks exactly like the study drug but contains no active drug). Participants will be required to schedule weekly office visits throughout Phase II.
Subjects who complete the 15-week trial (both Phases I and II) will enter the 6-Month Follow-Up to evaluate rates of long term abstinence from nicotine. They will have office visits at Weeks 20, 24, 28, 32, 36, and 40 after discontinuation of study medications.
Participants who enter the study will be offered the opportunity to participate in an ancillary neuroimaging study of mechanisms and surrogate markers of relapse that includes BOLD fMRI and MR spectroscopy, to be carried out at the McLean Brain Imaging Center.
|United States, Massachusetts|
|McLean Hospital, Brain Imaging Center|
|Belmont, Massachusetts, United States, 02478 9106|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Maurizio Fava, M.D.||Massachusetts General Hospital|
|Principal Investigator:||Eden Evins, M.D., M.P.H.||Massachusetts General Hospital|