A Phase 1/2 interventional study of zonisamide and placebo in Nicotine Dependence, sponsored by Johns Hopkins University. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-01-24.
Sponsored by Johns Hopkins University · Phase 1/2, Interventional, and Treatment
Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking cessation.
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.
968 studies on the registry are indexed under Tobacco Use Disorder; 126 are open to participants now.
This study's enrollment of 74 is below the median of 89 across 851 interventional studies indexed under Tobacco Use Disorder.
Browse Tobacco Use Disorder studies →Johns Hopkins University is the lead sponsor of 1,783 studies on the registry; 313 are open to participants now.
Of its 203 completed or terminated interventional studies of FDA-regulated products, 140 (69%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
participants will receive zonisamide capsules (up to 300 mg) to take once a day.
Drug: zonisamide
Participants will receive placebo capsules to take once a day
Drug: placebo
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
Also known as: zonegran®
Percent Participants Abstinent From Smoking During Study Weeks 7-10
Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.
Time frame: weeks 7-10
Nicotine Withdrawal Symptom Severity
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.
Time frame: Past 24 hours
| Milestone | Zonisamide | Placebo |
|---|---|---|
| Started | 34 | 40 |
| Completed | 18 | 27 |
| Not completed | 16 | 13 |
Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.
| Participants | Zonisamide | Placebo |
|---|---|---|
| Percent Participants Abstinent From Smoking During Study Weeks 7-10 | 5 | 6 |
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.
| units on a scale | Zonisamide | Placebo |
|---|---|---|
| Screening Visit | 4.6 ± 6.0 | 5.6 ± 5.5 |
| Admission Visit | 5.1 ± 5.3 | 7.0 ± 6.3 |
| Week 1 (pre-quit day) | 5.3 ± 6. | 6.2 ± 7.3 |
| Week 2 (pre-quit day) | 4.8 ± 6.0 | 5.7 ± 6.3 |
| Week 3 (target quit day) | 4.7 ± 5.4 | 6.6 ± 7.0 |
| Week 4 | 3.8 ± 5.1 | 5.9 ± 7.0 |
| Week 5 | 3.8 ± 3.7 | 4.7 ± 5.3 |
| Week 6 | 3.4 ± 4.3 | 4.0 ± 5.0 |
| Week 7 | 3.8 ± 4.7 | 4.4 ± 4.7 |
| Week 8 | 2.7 ± 3.3 | 4.0 ± 4.5 |
| Week 9 | 3.1 ± 3.0 | 4.1 ± 4.4 |
| Week 10 | 2.6 ± 4.9 | 4.8 ± 5.8 |
Collected over Adverse events were collected systematically during each study visit for the duration of the 10-week study. All events that were rated as being possibly, probably, or definitely related to study participation are reported. Events can represent nicotine withdrawal symptoms (e.g. all events were documented and nicotine withdrawal symptoms were not excluded from Adverse Events (AE) reporting).. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Zonisamide | 0/34 (0%) | 0/34 (0%) | 28/34 (82.4%) |
| Placebo | 0/40 (0%) | 0/40 (0%) | 28/40 (70%) |
| Event | Zonisamide | Placebo |
|---|---|---|
| NauseaGastrointestinal disorders | 11/34 | 11/40 |
| Dream AbnormalNervous system disorders | 8/34 | 7/40 |
| InsomniaNervous system disorders | 7/34 | 3/40 |
| DrowsinessNervous system disorders | 6/34 | 4/40 |
| IrritabilityNervous system disorders | 6/34 | 7/40 |
| HeadacheGeneral disorders | 5/34 | 4/40 |
| ConstipationGastrointestinal disorders | 5/34 | 4/40 |
| VomitingGastrointestinal disorders | 4/34 | 2/40 |
| Sweating IncreasedSkin and subcutaneous tissue disorders | 3/34 | 0/40 |
| AgitationNervous system disorders | 3/34 | 1/40 |
| Age, Continuous(years) | Zonisamide | Placebo | Total |
|---|---|---|---|
| Mean | 45.3 ± 9.8 | 45.9 ± 9.7 | 45.6 ± 9.8 |
| Sex: Female, Male(Participants) | Zonisamide | Placebo | Total |
|---|---|---|---|
| Female | 8 | 13 | 21 |
| Male | 26 | 27 | 53 |
| Ethnicity (NIH/OMB)(Participants) | Zonisamide | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 1 |
| Not Hispanic or Latino | 34 | 39 | 73 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Zonisamide | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 23 | 27 | 50 |
| White | 11 | 13 | 24 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Zonisamide | Placebo | Total |
|---|---|---|---|
| United States | 34 | 40 | 74 |
This study is completed, as verified in Jan 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Johns Hopkins University