Alcohol Use DisordersPhase 2ZNSBPNCT01566370
Zonisamide for Heavy Drinkers With Bipolar Disorder
A Phase 2 study testing Zonisamide in people with Alcohol Use Disorders and Bipolar Disorder, run by Yale University at 1 site in United States.
Trial summary
This is a randomized, double blind, placebo controlled trial of the medication zonisamide for the purpose of reducing heavy drinking and drinking, as well as reducing mood symptoms, in bipolar subjects that drink excessively and heavily. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Use Disorders, Bipolar Disorder
- 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
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Jul 2013
- Phase
- Phase 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
- Female/male aged 18-65 years
- Ability to provide informed consent to participate
- Presence of Axis I diagnosis of BD (either type I, Type II, or NOS), in manic, hypomanic, depressive, mixed, or euthymic states plus presence of Axis I diagnosis of a current AUD and/or "at risk" regular heavy drinking (must average >2 heavy drinking days per week) with the goal of reducing or stopping drinking
- treatment with a standard mood stabilizer medication and or other medications with known psychotropic effects on mood state but not alcohol use; Lithium, and/or atypical antipsychotic medications will be the preferred medications,
- Subjects not on any primary acceptable mood stabilizer as described above must be willing to begin treatment with Lithium in open label fashion,
- English speaking, Able to read at the eighth grade or higher level and show no evidence of significant cognitive impairment;
- Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or tubal ligation or <2 years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative serum pregnancy test prior to initiation of treatment;
- Must continue to have at least 2 heavy drinking days per week (averaged per month, with heavy drinking defined as having >4 standard drinks per day for males, and >3 standard drinks per day for females) up to the screening appointment
Who cannot join
- Presence of another major Axis I disorder such as Schizophrenia or Schizoaffective disorder, Delusional disorder, or other severe psychiatric disorder. A history of suicidal or violent behavior which, in the opinion of the study physician, puts the patient at significant risk of suicide or homicide during the study.
- Past history of drug abuse or dependence will be allowed, but active drug dependence (with the exception of nicotine dependence) in the last 30 days will be disqualifying.
- Serious neurological, or endocrine disorder,
- Evidence of potentially serious or as yet undiagnosed medical problems,
- Neurocognitive cognitive or language limitations, or other incapacity with providing informed consent;
- Known adverse reaction to zonisamide, sulfa-drug allergy, penicillin allergy, other severe adverse drug reaction or allergy, or any serious systemic autoimmune illness,
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- Patients currently undergoing ECT treatment.
- Also patients with a history of seizures (other than febrile seizures), renal calculi, or currently taking medications that could either significantly increase the risk of seizures (e.g., tricyclic antidepressant agents, Bupropion, clozaril), or that could potentially theoretically significantly influence drinking behavior such as benzodiazepines, stimulants, opioid painkillers, sedative-hypnotics, etc.).
- Subjects on the following anticonvulsant medications will also be excluded as they may increase the risk of similar side-effects (similar to zonisamide) such as rash, cognitive impairment, or potentially could confound the study of drinking behavior; topiramate, tiagabine, oxcarbazepine, carbamezapine, valproic acid, lamotrigine
- Patients who, on clinical examination by a physician, are deemed to be too severely alcohol dependent to permit them to participate in an outpatient level of care medication trial. We have, over the years, developed methods for reliably and safely assessing patients for alcohol treatment and dual diagnosis studies.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Healthcare System
West Haven, Connecticut, 06516
About this study
This is a randomized, double blind, placebo controlled trial of the medication zonisamide for the purpose of reducing heavy drinking and drinking, as well as reducing mood symptoms, in bipolar subjects that drink excessively and heavily.
Hypotheses: (Primary aims); Add-on zonisamide compared to placebo will result in:
Read more
- significant reduction in heavy drinking days, drinks per week and per drinking day, and significantly greater increase in abstinent days, ii) greater rates of abstinence and abstinence to heavy drinking, greater reduction in biomarkers of heavy alcohol use such as gamma-glutamyl transferase (GGT), and greater reduction in alcohol urge or "craving",
- Significant reduction in prevalent mood symptoms on the BRMS and BRMeS, CARS, HAMD, or no worsening of euthymic mood, and significant improvement on the Clinical Global Impressions Scale-Severity.
- (Secondary aims) Add-on zonisamide compared to placebo will result in significant reduction in weight (kilograms) and other secondary weight-related metabolic factors such as fasting glucose, lipid profile, and blood pressure.
- (Secondary aims) Add-on zonisamide compared to placebo will result in improved clinical global impression, overall functioning, quality of life, and reduced medical symptoms.
5.) (Exploratory Aims) To will examine interactions between genotype and medication on treatment response for allelic variation in genetic loci related to the major neurotransmitter and neurophysiologic pathways that are relevant to bipolar disorder, alcoholism, and zonisamide mechanism of action.
- Conditions
- Alcohol Use Disorders, Bipolar Disorder
- Being tested
- Zonisamide, Placebo
- Keywords
- alcoholism, alcohol use disorder, alcohol dependence, alcohol abuse, bipolar, anticonvulsant, zonisamide
- Medical subject headings
- Alcoholism, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZonisamideDrug
Also called Zonegran
titration of dose to 500mg oral, daily, over 8 weeks, then 6 weeks of treatment at that dose
PlaceboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| Zonisamide | Experimental | Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind Receives: Drug: Zonisamide |
| Placebo | Placebo comparator | Patients will receive placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Total Heavy Drinking Days
The percentage of total heavy drinking days compared between groups (zonisamide and placebo) during the time spent on the target dose of the medication (i.e., not including the titration or taper periods), totaled between the time-points of weeks 11 and 14 (4 weeks time frame).
Measured: from week 11 through 14 (over 4 weeks)
Change on Hamilton Depression Rating Scale
Change from baseline to endpoint in Hamilton scores compared between medication and placebo, using repeated measures
Measured: 14 weeks
Change in Clinician Assisted Rating Scale for Mania (CARS-M) Scores
Comparison between groups on change in scores on the CARS-M over 14 weeks from baseline to endpoint, measured weekly and analyzed with repeated measures
Measured: 14 weeks
Secondary outcomes (7)
Percentage of Abstinent Days
The difference in total percentage of abstinent compared between groups (zonisamide and placebo) during the time spent on the target dose of the medication (i.e., not including the titration or taper periods), which includes week 11, 12, 13, and 14.
Measured: over four weeks, from week 11 through 14
Change in Alcohol Urge Questionnaire Score
This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures
Measured: from baseline to endpoint, 14 weeks
Change in Gamma Glutamyl Transferase (GGT)
Difference between groups on change in levels of GGT over time, measured at baseline, week 5, week 9, week 13, and endpoint, using repeated measures
Measured: 14 weeks
Change in Beck Depression Inventory (BDI) Scores
Comparison between groups on change in BDI scores over the 14 weeks of the study, measured weekly, using repeated measures
Measured: 14 weeks
Percentage of Total Drinking Days
The percentage of total drinking days compared between groups (zonisamide and placebo) during the time spent on the target dose of the medication (i.e., not including the titration or taper periods), which includes week 11, 12, 13, and 14.
Measured: 4 weeks
Change in Number of Heavy Drinking Days Per Week by Time
A comparison between medication and placebo on the measure of number heavy drinking days per week over the course of the study (baseline to endpoint) via interaction with time using repeated measures
Measured: 14 weeks (baseline to endpoint)
Change in Number of Drinks Per Week by Time
Comparison between medication and placebo groups on the change in number of drinks per week via interaction with time (from baseline to endpoint) using repeated measures
Measured: 14 weeks (baseline to endpoint)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study startMay 2012
- Primary completionJul 2013
- Study completionJul 2013
Why it stopped: recruitment infeasible
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.
- Other trials for Alcohol Use DisordersStudies of the same condition, open and under way.
- More trials run by Yale 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Albert J Arias, MD, Principal investigator, Yale University, VA CT Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01566370
- Sponsor's protocol ID
- ZNS-BP
- Other IDs
- VACT MIRECC, K23AA017689
- Acronym
- ZNSBP
- Status last verified
- Nov 2016
- First submitted
- 15 Dec 2011
- Last updated
- 13 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zonisamide for Heavy Drinkers With Bipolar Disorder
- ClinicalTrials.gov ID
- NCT01566370
- Acronym / sponsor ID
- ZNSBP / ZNS-BP
- Conditions
- Alcohol Use Disorders, Bipolar Disorder
- Keywords
- alcoholism, alcohol use disorder, alcohol dependence, alcohol abuse, bipolar, anticonvulsant, zonisamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment infeasible
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- May 2012
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 29 Mar 2012 (estimated)
- Results
- Posted 22 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double blind, placebo controlled trial of the medication zonisamide for the purpose of reducing heavy drinking and drinking, as well as reducing mood symptoms, in bipolar subjects that drink excessively and heavily.
Hypotheses: (Primary aims); Add-on zonisamide compared to placebo will result in:
- significant reduction in heavy drinking days, drinks per week and per drinking day, and significantly greater increase in abstinent days, ii) greater rates of abstinence and abstinence to heavy drinking, greater reduction in biomarkers of heavy alcohol use such as gamma-glutamyl transferase (GGT), and greater reduction in alcohol urge or "craving",
- Significant reduction in prevalent mood symptoms on the BRMS and BRMeS, CARS, HAMD, or no worsening of euthymic mood, and significant improvement on the Clinical Global Impressions Scale-Severity.
- (Secondary aims) Add-on zonisamide compared to placebo will result in significant reduction in weight (kilograms) and other secondary weight-related metabolic factors such as fasting glucose, lipid profile, and blood pressure.
- (Secondary aims) Add-on zonisamide compared to placebo will result in improved clinical global impression, overall functioning, quality of life, and reduced medical symptoms.
5.) (Exploratory Aims) To will examine interactions between genotype and medication on treatment response for allelic variation in genetic loci related to the major neurotransmitter and neurophysiologic pathways that are relevant to bipolar disorder, alcoholism, and zonisamide mechanism of action.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zonisamide | Experimental | Drug: ZonisamideSubjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive placebo pills that are made to match the zonisamide medication (via over-encapsulation, double-blind, subjects will receive same number of capsules as the active medication group |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Female/male aged 18-65 years
- Ability to provide informed consent to participate
- Presence of Axis I diagnosis of BD (either type I, Type II, or NOS), in manic, hypomanic, depressive, mixed, or euthymic states plus presence of Axis I diagnosis of a current AUD and/or "at risk" regular heavy drinking (must average >2 heavy drinking days per week) with the goal of reducing or stopping drinking
- treatment with a standard mood stabilizer medication and or other medications with known psychotropic effects on mood state but not alcohol use; Lithium, and/or atypical antipsychotic medications will be the preferred medications,
- Subjects not on any primary acceptable mood stabilizer as described above must be willing to begin treatment with Lithium in open label fashion,
Key exclusion criteria (10 listed)
- Presence of another major Axis I disorder such as Schizophrenia or Schizoaffective disorder, Delusional disorder, or other severe psychiatric disorder. A history of suicidal or violent behavior which, in the opinion of the study physician, puts the patient at significant risk of suicide or homicide during the study.
- Past history of drug abuse or dependence will be allowed, but active drug dependence (with the exception of nicotine dependence) in the last 30 days will be disqualifying.
- Serious neurological, or endocrine disorder,
- Evidence of potentially serious or as yet undiagnosed medical problems,
- Neurocognitive cognitive or language limitations, or other incapacity with providing informed consent;
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: Zonegrantitration of dose to 500mg oral, daily, over 8 weeks, then 6 weeks of treatment at that dose | Drug | Zonisamide |
| Placeboplacebo | Drug | Placebo |
Primary outcome
Percentage of Total Heavy Drinking Days
Time frame: from week 11 through 14 (over 4 weeks)
The percentage of total heavy drinking days compared between groups (zonisamide and placebo) during the time spent on the target dose of the medication (i.e., not including the titration or taper periods), totaled between the time-points of weeks 11 and 14 (4 weeks time frame).
Change on Hamilton Depression Rating Scale
Time frame: 14 weeks
Change from baseline to endpoint in Hamilton scores compared between medication and placebo, using repeated measures
Change in Clinician Assisted Rating Scale for Mania (CARS-M) Scores
Time frame: 14 weeks
Comparison between groups on change in scores on the CARS-M over 14 weeks from baseline to endpoint, measured weekly and analyzed with repeated measures
7 secondary outcomes
Percentage of Abstinent Days
Time frame: over four weeks, from week 11 through 14
Change in Alcohol Urge Questionnaire Score
Time frame: from baseline to endpoint, 14 weeks
Change in Gamma Glutamyl Transferase (GGT)
Time frame: 14 weeks
Change in Beck Depression Inventory (BDI) Scores
Time frame: 14 weeks
Percentage of Total Drinking Days
Time frame: 4 weeks
Change in Number of Heavy Drinking Days Per Week by Time
Time frame: 14 weeks (baseline to endpoint)
Change in Number of Drinks Per Week by Time
Time frame: 14 weeks (baseline to endpoint)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Albert J Arias, MD principal investigator
Yale University, VA CT Health System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zonisamide in people with Alcohol Use Disorders and Bipolar Disorder, run by Yale 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 8 inclusion and 10 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: stopped early, as of the sponsor's last update on 13 Jan 2017. 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 phase mean?
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 22 Apr 2016). 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?
Percentage of Total Heavy Drinking Days (time frame: from week 11 through 14 (over 4 weeks)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2017.