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Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation (1207)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01685996
Recruitment Status : Completed
First Posted : September 17, 2012
Results First Posted : June 5, 2017
Last Update Posted : January 24, 2018
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE September 12, 2012
First Posted Date  ICMJE September 17, 2012
Results First Submitted Date  ICMJE April 17, 2017
Results First Posted Date  ICMJE June 5, 2017
Last Update Posted Date January 24, 2018
Study Start Date  ICMJE September 2012
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
Percent Participants Abstinent From Smoking During Study Weeks 7-10 [ Time Frame: weeks 7-10 ]
Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.
Original Primary Outcome Measures  ICMJE
 (submitted: September 14, 2012)
smoking abstinence [ Time Frame: weeks 7-10 ]
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2017)
Nicotine Withdrawal Symptom Severity [ Time Frame: Past 24 hours ]
Total Score from the Minnesota Nicotine Withdrawal Questionnaire (MNWQ), assessed at weekly visits. The MNWQ is a commonly-used 12-item Likert scale self-report measure of nicotine symptoms. Individual symptoms were rated from 0 (none) to 4 (severe) for each item and the Total score range was 0 - 48. Ratings were collected once weekly during study visits.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2012)
Nicotine Withdrawal Symptom Severity [ Time Frame: weeks 3-10 ]
nicotine withdrawal symptoms will be monitored weekly
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: September 14, 2012)
sleep quality [ Time Frame: weeks 3-10 ]
sleep diary will be kept, and self-reported sleep quality will be measured weekly
Descriptive Information
Brief Title  ICMJE Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
Official Title  ICMJE Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Nicotine Dependence
Intervention  ICMJE
  • Drug: zonisamide
    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®
  • Drug: placebo
Study Arms  ICMJE
  • Experimental: zonisamide
    participants will receive zonisamide capsules (up to 300 mg) to take once a day.
    Intervention: Drug: zonisamide
  • Placebo Comparator: Placebo
    Participants will receive placebo capsules to take once a day
    Intervention: Drug: placebo
Publications * Dunn KE, Marcus TF, Kim C, Schroeder JR, Vandrey R, Umbricht A. Zonisamide Reduces Withdrawal Symptoms But Does Not Enhance Varenicline-Induced Smoking Cessation. Nicotine Tob Res. 2016 May;18(5):1171-9. doi: 10.1093/ntr/ntv236. Epub 2015 Oct 17.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 30, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: September 14, 2012)
Actual Study Completion Date  ICMJE May 2014
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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., trimethoprim/sulfamethoxazole, zonisamide or topiramate);
  • Renal insufficiency (eGFR < 60 mL)
  • Renal tubular acidosis
  • History of nephrolithiasis
  • Unexplained hematuria
  • Transaminase elevations > 3 times the Upper Limit of Normal (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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01685996
Other Study ID Numbers  ICMJE NA_00074143
R21DA034164 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE National Institute on Drug Abuse (NIDA)
Investigators  ICMJE
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
PRS Account Johns Hopkins University
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP