Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): zonisamide; placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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 intervention name(s): zonegran®
Intervention MeSH terms: Zonisamide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: tobacco; smoking cessation; nicotine; cigarettes; nicotine withdrawal