The Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette

February 4, 2026 updated by: Rose Research Center, LLC

A Randomized Controlled Trial to Determine the Effects of Combination Zonisamide and Bupropion on Switching to an Electronic Cigarette

This three-group randomized double-blind placebo-controlled trial (N=180) will evaluate the impact of combination zonisamide and bupropion on the process of switching from combustible cigarettes (CCs) to an e-cigarette. There will be a data collection period of at least five days to obtain baseline information on the use of combustible cigarettes. All participants enrolled in the study will receive a JUUL e-cigarette at Visit 2 for ad libitum use. After the first week of e-cigarette use (at Visit 3), participants will be given bupropion (150 mg each morning for days 1-3, then 300 mg daily) with either zonisamide (100 mg daily) or placebo (group 1 and group 2 respectively), or placebo for both medications (group 3) in addition to continued use of the e-cigarette. At each visit, participants will receive enough study drugs (or placebos) and e-cigarettes to last until their next study visit. The combination of zonisamide and bupropion use will continue until Visit 6 (7 weeks of treatment), and e-cigarette use will continue until the end of treatment (Visit 7).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
180

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • North Carolina
      • Charlotte, North Carolina, United States, 28262
        • Rose Research Center
      • Raleigh, North Carolina, United States, 27617
        • Rose Research Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Has signed the ICF and is able to read and understand the information provided in the ICF.
  2. Is 21 to 65 years of age (inclusive) at screening.
  3. Smokes at least 10 commercially available cigarettes per day (no brand restrictions), for the last 12 months.
  4. Has an expired air CO reading of at least 10 ppm at screening.
  5. Is interested in switching to an electronic cigarette.
  6. Is willing and able to comply with the requirements of the study.
  7. Owns a smartphone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria:

  1. Is unhealthy or cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) as judged by the Investigator or designated medical staff based on all available assessments from the screening period (e.g., safety laboratory, vital signs, physical examination, ECG, concomitant medications and medical history).
  2. Has a PHQ-9 score greater than 9, or a score greater than 0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") at screening.
  3. Has plans to use an FDA-approved smoking cessation product during the study.
  4. Has high blood pressure (systolic > 150 mmHg or diastolic >95 mmHg) at screening.
  5. Has body mass index (BMI) less than 15.0 kg/m2 or greater than 40.0 kg/m2.
  6. Has coronary heart disease, structural cardiac disease (including, but not limited to valvular heart disease or cardiac murmurs), cardiac dysrhythmias, syncope, cardiac chest pain, or history of heart attack or heart failure.
  7. Has received psychotherapy or behavioral treatments potentially impacting symptoms of depression, anxiety, or nicotine withdrawal within 30 days of screening, or during the study.
  8. Is taking antidepressants, psychoactive medications (e.g. antipsychotics, benzodiazepines, hypnotics) or medications that prolong QTc.

  9. Has used any of these products in the past 30 days:

    1. Illegal drugs (or if the urine drug screen is positive for cocaine, THC, amphetamines, methamphetamines, or opiates);
    2. Experimental (investigational) drugs that are unknown to participant;
    3. Chronic opiate use.
  10. Has used smokeless tobacco (chewing tobacco, snuff), cigars (except for "Black & Mild" cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy or other smoking cessation treatments within 14 days of screening.
  11. Has a plan to use an FDA-approved quit-smoking treatment in the next 30 days.
  12. Is pregnant or nursing (by self-report) or has a positive pregnancy test.
  13. Enrollment requirements met.

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: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Combination zonisamide and bupropion with e-cigarette
After the first week of e-cigarette use (JUUL), participants will be given bupropion (150 mg each morning for days 1-3, then 300 mg daily) with zonisamide (100 mg daily). The combination of zonisamide and bupropion use will continue for 7 weeks of treatment, and e-cigarette use will continue until the end of the study (an additional 4 weeks).
Drug: Bupropion
Extended-release bupropion dosing (150 mg each morning days 1-3, then 300 mg/daily) for the remainder of the 7 weeks.
Other Names:
  • Wellbutrin
  • Zyban
Drug: Zonisamide
Zonisamide (100 mg/daily) for 7 weeks.
Other Names:
  • zonegran
Other: E-cigarette
e-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks.
Other Names:
  • JUUL
Experimental: Bupropion with e-cigarette
After the first week of e-cigarette use (JUUL), participants will be given bupropion (150 mg each morning for days 1-3, then 300 mg daily) with placebo zonisamide. The combination of placebo and bupropion use will continue for 7 weeks of treatment, and e-cigarette use will continue until the end of the study (an additional 4 weeks).
Drug: Bupropion
Extended-release bupropion dosing (150 mg each morning days 1-3, then 300 mg/daily) for the remainder of the 7 weeks.
Other Names:
  • Wellbutrin
  • Zyban
Other: E-cigarette
e-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks.
Other Names:
  • JUUL
Drug: Placebo zonisamide
Placebo zonisamide for 7 weeks.
Placebo Comparator: Placebo with e-cigarette
After the first week of e-cigarette use (JUUL), participants will be given placebo bupropion with placebo zonisamide. The combination of these placebos will continue for 7 weeks of treatment, and e-cigarette use will continue until the end of the study (an additional 4 weeks).
Other: E-cigarette
e-cigarette for ad libitum use for two weeks prior to complete switch day and for an additional 10 weeks.
Other Names:
  • JUUL
Drug: Placebo zonisamide
Placebo zonisamide for 7 weeks.
Drug: Placebo bupropion
Placebo bupropion for 7 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by Exhaled carbon monoxide (CO)
Time Frame: After 8 weeks
Exhaled carbon monoxide (CO) < 5 ppm at the end of drug treatment
After 8 weeks
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by change in Total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
Time Frame: Baseline, Week 8, Week 12
Total urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)
Baseline, Week 8, Week 12
Complete Switching From Combustible Cigarettes to JUUL e-cigarette as measured by change in self-report of daily cigarette and e-cigarette use
Time Frame: Daily from Week 2 to Week 12
Self-report of daily cigarette and e-cigarette use
Daily from Week 2 to Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Smoking withdrawal symptoms
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Smoking withdrawal symptoms will be collected using a questionnaire developed by Drs. Shiffman and Jarvik (1976), which assesses craving for cigarettes, negative mood, arousal, missing the habit of smoking, changes in appetite and somatic symptoms and a seven-point scale (from 1-Not at All to 7-Extremely). Higher scores indicate more withdrawal symptoms.
Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
Change in Rewarding and aversive effects of smoking and e-cigarette use
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12
The mCEQ-E will be utilized to assess the degree to which participants experience the reinforcing of smoking, providing five subscale scores: smoking satisfaction (satisfying, tastes good,enjoy smoking), psychological rewards (calms down, more awake, less irritable, helps concentrate, reduces hunger), aversion (dizziness, nauseated), enjoyment of respiratory tract sensations (single-item assessment), craving reduction (single-item assessment). Participants will be asked to assess the 12 items of the questionnaire on a 7-point scale, ranging from "not at all" to "extremely". These 12 items will be asked for the "first cigarette smoked", "cigarette immediately after a meal", and "all other cigarettes." The e-cigarette version of this questionnaire (mECEQ-E) will also be used.
Baseline, Week 1, Week 2, Week 4, Week 8, Week 12

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Tolerability of study drugs as measured by frequency of drug termination or drug non-adherence
Time Frame: Baseline, Week 1, Week 2, Week 4, Week 8
The frequency of drug termination or non-adherence prior to Week 8 will be tabulated for each condition. Adverse effects will also be tabulated for each condition, including the following adverse effects of special interest (AESIs): insomnia, agitation, dry mouth, somnolence, headache, nausea, constipation, diarrhea, dizziness or loss of appetite.
Baseline, Week 1, Week 2, Week 4, Week 8
Seven-day point abstinence at 6 months post-switch
Time Frame: 6 Months post Switch Day
Seven-day point abstinence at 6 months post-switch will be assessed by self-report and confirmed by exhaled carbon monoxide (CO) < 5 ppm.
6 Months post Switch Day

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rose Research Center, LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Foundation for a Smoke Free World INC

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 (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 14, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 19, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 13, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 27, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BuZonE 2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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