Nicotine DependencePhase 1/21207NCT01685996
Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
A Phase 1/2 study testing zonisamide in people with Nicotine Dependence, run by Johns Hopkins University at 1 site in United States.
Trial summary
Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking cessation. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- zonisamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to May 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 20Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Behavioral Pharmacology Research Unit
Baltimore, Maryland, 21224
About this study
Randomized trial to evaluate whether zonisamide can enhance varenicline-induced smoking cessation.
Read the 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.
- Conditions
- Nicotine Dependence
- Being tested
- zonisamide, placebo
- Keywords
- tobacco, smoking cessation, nicotine, cigarettes, nicotine withdrawal
- Medical subject headings
- Tobacco Use Disorder, Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zonisamideDrug
Also called zonegran®
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
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| zonisamide | Experimental | participants will receive zonisamide capsules (up to 300 mg) to take once a day. Receives: Drug: zonisamide |
| Placebo | Placebo comparator | Participants will receive placebo capsules to take once a day Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Participants Abstinent From Smoking During Study Weeks 7-10
Biochemically-verified continuous smoking abstinence during weeks 7-10 of the study.
Measured: weeks 7-10
Secondary outcomes (1)
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.
Measured: Past 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2012 (estimated)
- Study startSep 2012
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Annie Umbricht, M.D., Principal investigator, 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01685996
- Sponsor's protocol ID
- NA_00074143
- Other IDs
- R21DA034164
- Acronym
- 1207
- Status last verified
- Jan 2018
- First submitted
- 12 Sep 2012
- Last updated
- 24 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 26476459
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zonisamide Augmentation of Varenicline Treatment for Smoking Cessation
- ClinicalTrials.gov ID
- NCT01685996
- Acronym / sponsor ID
- 1207 / NA_00074143
- Conditions
- Nicotine Dependence
- Keywords
- tobacco, smoking cessation, nicotine, cigarettes, nicotine withdrawal
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- Sep 2012
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 17 Sep 2012 (estimated)
- Results
- Posted 5 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| zonisamide | Experimental | Drug: zonisamideparticipants will receive zonisamide capsules (up to 300 mg) to take once a day. |
| Placebo | Placebo comparator | Drug: placeboParticipants will receive placebo capsules to take once a day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zonisamideAlso: zonegran®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 | Drug | zonisamide |
| placebo | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
Nicotine Withdrawal Symptom Severity
Time frame: Past 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26476459Dunn 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annie Umbricht, M.D. principal investigator
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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing zonisamide in people with Nicotine Dependence, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Participants Abstinent From Smoking During Study Weeks 7-10 (time frame: weeks 7-10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01685996, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2018.