Zonisamide for Heavy Drinkers With Bipolar Disorder (ZNSBP)

This study is currently recruiting participants.
Verified January 2013 by VA Connecticut Healthcare System
Sponsor:
Collaborator:
Information provided by (Responsible Party):
VA Connecticut Healthcare System
ClinicalTrials.gov Identifier:
NCT01566370
First received: December 15, 2011
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Alcohol Use Disorders
Bipolar Disorder
Drug: Zonisamide
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zonisamide for Heavy Drinkers With Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by VA Connecticut Healthcare System:

Primary Outcome Measures:
  • Percentage of total Heavy Drinking Days [ Time Frame: from week 11 through 14 (over 4 weeks) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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:
  • Percentage of Abstinent Days [ Time Frame: over four weeks, from week 11 through 14 ] [ Designated as safety issue: No ]
    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.

  • Change in Alcohol Urge Questionnaire Score [ Time Frame: from baseline to endpoint, 14 weeks ] [ Designated as safety issue: No ]
    This is the change in AUQ scores (urge to drink) measured weekly compared between groups using repeated measures

  • Change in Gamma glutamyl transferase (GGT) [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    Difference between groups on change in levels of GGT over time, measured at baseline, week 5, week 9, week 13, and enpoint, using repeated measures

  • Change in Beck Depression Inventory (BDI) Scores [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    Comparison between groups on change in BDI scores over the 14 weeks of the study, measured weekly, using repeated measures

  • Percentage of total drinking days [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in number of heavy drinking days per week by time [ Time Frame: 14 weeks (baseline to endpoint) ] [ Designated as safety issue: No ]
    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

  • Change in number of drinks per week by time [ Time Frame: 14 weeks (baseline to endpoint) ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 40
Study Start Date: May 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
placebo
Other Name: placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01566370

Contacts
Contact: Albert J Arias, MD 2039325711 ext 8155 albert.arias@yale.edu
Contact: Diana Limoncelli, BS 2039325711 ext 5217 diana.limoncelli@yale.edu

Locations
United States, Connecticut
VA Connecticut Healthcare System Recruiting
West Haven, Connecticut, United States, 06516
Contact: Albert Arias, MD    203-932-5711 ext 4471    albert.aria@yale.edu   
Sponsors and Collaborators
VA Connecticut Healthcare System
Investigators
Principal Investigator: Albert J Arias, MD Yale University, VA CT Health System
  More Information

No publications provided

Responsible Party: VA Connecticut Healthcare System
ClinicalTrials.gov Identifier: NCT01566370     History of Changes
Other Study ID Numbers: ZNS-BP, VACT MIRECC, K23AA017689
Study First Received: December 15, 2011
Last Updated: January 14, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by VA Connecticut Healthcare System:
alcoholism
alcohol use disorder
alcohol dependence
alcohol abuse
bipolar
anticonvulsant
zonisamide

Additional relevant MeSH terms:
Alcohol Drinking
Alcoholic Intoxication
Bipolar Disorder
Drinking Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Affective Disorders, Psychotic
Mood Disorders
Zonisamide
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014