This trial is active, not recruiting.

Condition nicotine dependence
Treatments zonisamide, placebo
Phase phase 1/phase 2
Sponsor Johns Hopkins University
Start date September 2012
End date May 2014
Trial size 200 participants
Trial identifier NCT01685996, R21 DA034164


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
participants will receive zonisamide capsules (up to 300 mg) to take once a day.
zonisamide zonegran®
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
(Placebo Comparator)
Participants will receive placebo capsules to take once a day

Primary Outcomes

smoking abstinence
time frame: weeks 7-10

Secondary Outcomes

nicotine withdrawal symptom severity
time frame: weeks 3-10

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Ages 18 - 65 years old; smoking > 10 cigarettes per day for > 1 year - Desire to quit smoking - Provide a cotinine positive urine sample - Commitment to come to the clinic once a week for the 10-week study duration Exclusion Criteria: - Allergy to varenicline or sulfonamide drugs (e.g., trimetoprim/sulfamethoxazole, zonisamide or topiramate); - Renal insufficiency (eGFR < 60 mL) - Renal tubular acidosis - History of nephrolithiasis - Unexplained hematuria - Transaminase elevations > 3 times the ULN - BMI < 19 - Diabetes mellitus - Respiratory insufficiency - Asthma requiring medication - Heart failure - Chronic diarrhea predisposing to acidosis - Glaucoma, family history of glaucoma, one-sided blindness - History of seizures or use of anticonvulsant medications (not including sedatives) - HIV infection on HAART medication (or CD4 T cell count < 200 /mL) - History of serious psychiatric disorder: psychosis, dementia, depression requiring medication in last 6 months, suicidal or homicidal ideation, evidence of violent behavior in the last 6 months. - Recent use (last 30 days) of bupropion, nortriptyline, or clonidine - Recent use (last 30 days) of Nicotine Replacement Products that would interfere with urine cotinine testing - Use of tobacco products other than cigarettes - For female participants, pregnancy, lactation, or refusal to use an effective method of contraception.

Additional Information

Official title Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
Principal investigator Annie Umbricht, M.D.
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2014.
Information provided to ClinicalTrials.gov by Johns Hopkins University.