Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation (1207)

January 22, 2018 updated by: Johns Hopkins University
Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking cessation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

74

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Behavioral Pharmacology Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • zonegran®
Placebo Comparator: Placebo
Participants will receive placebo capsules to take once a day
Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
weeks 7-10

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Past 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

September 12, 2012

First Submitted That Met QC Criteria

September 14, 2012

First Posted (Estimate)

September 17, 2012

Study Record Updates

Last Update Posted (Actual)

January 24, 2018

Last Update Submitted That Met QC Criteria

January 22, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA_00074143
  • R21DA034164 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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