Clinical trial NCT01685996
Conditions: Nicotine Dependence
Keywords: tobacco smoking cessation nicotine cigarettes nicotine withdrawal
Sponsor: Johns Hopkins University
Start date: 2012-09-01; Completion date: 2014-05-01
Enrollment: 74 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking cessation.

Detailed description:
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 Gamma-Aminobutyric Acid (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.

Arms: arm 1: participants will receive zonisamide capsules (up to 300 mg) to take once a day. arm 2: Participants will receive placebo capsules to take once a day
Interventions: intervention 1: zonisamide intervention 2: placebo
Intervention descriptions: intervention 1: 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 intervention 2: None

Protocol documents: