Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation (1207)
About 20.6 % of the US population smokes cigarettes. This group includes nicotine dependent smokers who are resistant to current smoking cessation treatments. Varenicline is a smoking cessation medication found in meta-analytic reviews to be superior to other smoking cessation treatments, but 56% of patients who take varenicline do not quit. One strategy to increase quit rates may be to administer a second medication to augment the efficacy of varenicline. The anti-epileptic medication zonisamide is a good candidate for adjunct treatment as it increases dopaminergic tone, normalizes glutamate homeostasis, potentiates GABA release. Zonisamide improves sleep and promotes weight loss, two prominent issues not addressed by varenicline. Finally, the PI of this proposal has documented unpleasant changes in the taste of cigarettes and reductions in nicotine withdrawal among smokers receiving zonisamide as part of another clinical trial. The proposed study will explore the efficacy of varenicline + zonisamide for smoking cessation in a controlled, clinical trial. Eligible participants (n=60) will be smokers (>10 cig/day for >1 year) seeking treatment. They will be randomly assigned to receive varenicline + double-blind zonisamide or placebo for a 10-weeks. Participants will visit the clinic weekly to receive medications and smoking cessation counseling and to complete self-report questionnaires. Smoking status will be assessed via weekly urinalysis testing for cotinine (abstinence: <200ng/ml). Cotinine is a sensitive indicator of smoking status with a longer half-life then carbon monoxide (CO) and is more likely to detect low or intermittent smoking. The study hypothesis is that participants who receive the combination zonisamide + varenicline will achieve greater smoking abstinence compared to varenicline alone. The primary outcome measure will be the 4-week rate of biochemically-confirmed continuous smoking abstinence during weeks 7-10. Secondary outcomes will include self-reported rates of smoking, subjective effects of cigarettes, weight change from baseline to week 10, sleep quality, and nicotine withdrawal severity. This study will advance the science and clinical treatment of smoking cessation, and will provide the prerequisite data to develop a larger scale clinical trial evaluation of the combination zonisamide + varenicline for smoking cessation.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation|
- smoking abstinence [ Time Frame: weeks 7-10 ] [ Designated as safety issue: No ]The primary outcome measure for this study will be the 4-week rate of biochemically-confirmed continuous smoking abstinence during weeks 7-10 of the intervention
- nicotine withdrawal symptom severity [ Time Frame: weeks 3-10 ] [ Designated as safety issue: No ]nicotine withdrawal symptoms will be monitored weekly
- sleep quality [ Time Frame: weeks 3-10 ] [ Designated as safety issue: No ]sleep diary will be kept, and self-reported sleep quality will be measured weekly
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||May 2014|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
participants will receive zonisamide capsules (up to 300 mg) to take once a day.
In addition to zonisamide vs placebo treatment, varenicline tablets will be dispensed with specific instructions to take at the recommended doses for smoking cessation Participants will receive brief smoking cessation counseling and referral to a quitline
Other Name: zonegran®
Placebo Comparator: Placebo
Participants will receive placebo capsules to take once a day
Hughes JR, Rennard SI, Fingar JR, Talbot SK, Callas PW, Fagerstrom KO. Efficacy of varenicline to prompt quit attempts in smokers not currently trying to quit: A randomized placebo-controlled trial. Nicotine Tob Res. 2011 Oct; 13(10): 955-964.
Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2010 Dec 8; (12)(12): CD006103.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01685996
|United States, Maryland|
|Behavioral Pharmacology Research Unit|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||Annie Umbricht, M.D.||Assistant Professor Behavioral Pharmacology Research Unit The Johns Hopkins University School of Medicine 5510 Nathan Shock Drive Baltimore, MD 21224 tel: 410-550-1917 fax:410-550-0011 email@example.com|