Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation (1207)

• ClinicalTrials.gov Identifier: NCT01685996
• Recruitment Status: Completed
• First Posted: September 17, 2012
• Results First Posted: June 5, 2017
• Last Update Posted: January 24, 2018
• Sponsor: Johns Hopkins University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: September 12, 2012
• First Posted Date: September 17, 2012
• Results First Submitted Date: April 17, 2017
• Results First Posted Date: June 5, 2017
• Last Update Posted Date: January 24, 2018
• Study Start Date: September 2012
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Nicotine Dependence

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 30, 2017): 74
• Original Estimated Enrollment (submitted: September 14, 2012): 200
• Actual Study Completion Date: May 2014
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01685996
• Other Study ID Numbers: NA_00074143; R21DA034164 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Johns Hopkins University
• Study Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

• 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 annieumbricht@jhu.edu

• PRS Account: Johns Hopkins University
• Verification Date: January 2018