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Zonisamide for Heavy Drinkers With Bipolar Disorder (ZNSBP)

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ClinicalTrials.gov Identifier: NCT01566370
Recruitment Status : Terminated (recruitment infeasible)
First Posted : March 29, 2012
Results First Posted : April 22, 2016
Last Update Posted : January 13, 2017
Information provided by (Responsible Party):

Study Description
Brief 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.

Hypotheses: (Primary aims); Add-on zonisamide compared to placebo will result in:

  1. 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",
  2. 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.
  3. (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.
  4. (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.

Condition or disease Intervention/treatment Phase
Alcohol Use Disorders Bipolar Disorder Drug: Zonisamide Drug: Placebo Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zonisamide for Heavy Drinkers With Bipolar Disorder
Study Start Date : May 2012
Primary Completion Date : July 2013
Study Completion Date : July 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder
Drug Information available for: Zonisamide
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Zonisamide
Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind
Drug: Zonisamide
titration of dose to 500mg oral, daily, over 8 weeks, then 6 weeks of treatment at that dose
Other Name: Zonegran
Placebo Comparator: Placebo
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
Drug: Placebo

Outcome Measures

Primary Outcome Measures :
  1. 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).

  2. 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

  3. 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

Secondary Outcome Measures :
  1. Percentage of Abstinent Days [ Time Frame: over four weeks, from week 11 through 14 ]
    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.

  2. Change in Alcohol Urge Questionnaire Score [ Time Frame: from baseline to endpoint, 14 weeks ]
    This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures

  3. Change in Gamma Glutamyl Transferase (GGT) [ Time Frame: 14 weeks ]
    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

  4. Change in Beck Depression Inventory (BDI) Scores [ Time Frame: 14 weeks ]
    Comparison between groups on change in BDI scores over the 14 weeks of the study, measured weekly, using repeated measures

  5. Percentage of Total Drinking Days [ Time Frame: 4 weeks ]
    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.

  6. Change in Number of Heavy Drinking Days Per Week by Time [ Time Frame: 14 weeks (baseline to endpoint) ]
    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

  7. Change in Number of Drinks Per Week by Time [ Time Frame: 14 weeks (baseline to endpoint) ]
    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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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,
  • 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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01566370

United States, Connecticut
VA Connecticut Healthcare System
West Haven, Connecticut, United States, 06516
Sponsors and Collaborators
Yale University
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Principal Investigator: Albert J Arias, MD Yale University, VA CT Health System
More Information

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01566370     History of Changes
Other Study ID Numbers: ZNS-BP
VACT MIRECC ( Other Identifier: VA )
K23AA017689 ( U.S. NIH Grant/Contract )
First Posted: March 29, 2012    Key Record Dates
Results First Posted: April 22, 2016
Last Update Posted: January 13, 2017
Last Verified: November 2016

Keywords provided by Yale University:
alcohol use disorder
alcohol dependence
alcohol abuse

Additional relevant MeSH terms:
Bipolar Disorder
Alcohol Drinking
Alcoholic Intoxication
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs