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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

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

Condition or disease Intervention/treatment Phase
Nicotine Dependence Drug: zonisamide Drug: placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
Study Start Date : September 2012
Actual Primary Completion Date : May 2014
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: zonisamide
participants will receive zonisamide capsules (up to 300 mg) to take once a day.
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®

Placebo Comparator: Placebo
Participants will receive placebo capsules to take once a day
Drug: placebo

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01685996

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United States, Maryland
Behavioral Pharmacology Research Unit
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
National Institute on Drug Abuse (NIDA)
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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
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Johns Hopkins University Identifier: NCT01685996    
Other Study ID Numbers: NA_00074143
R21DA034164 ( U.S. NIH Grant/Contract )
First Posted: September 17, 2012    Key Record Dates
Results First Posted: June 5, 2017
Last Update Posted: January 24, 2018
Last Verified: January 2018
Keywords provided by Johns Hopkins University:
smoking cessation
nicotine withdrawal
Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs