Zonisamide for Heavy Drinkers With Bipolar Disorder

NCT ID: NCT01566370

Last Updated: 2017-01-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2013-07-31

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.

Conditions

Alcohol Use Disorders; Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Zonisamide

Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind

Group Type: EXPERIMENTAL

Zonisamide

Intervention Type: DRUG

titration of dose to 500mg oral, daily, over 8 weeks, then 6 weeks of treatment at that dose

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo

Interventions

Zonisamide

titration of dose to 500mg oral, daily, over 8 weeks, then 6 weeks of treatment at that dose

Intervention Type: DRUG

Placebo

placebo

Intervention Type: DRUG

Other Intervention Names

Zonegran

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert J Arias, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University, VA CT Health System

Locations

VA Connecticut Healthcare System

West Haven, Connecticut, United States

Countries

United States

Other Identifiers

VACT MIRECC

Identifier Type: OTHER

Identifier Source: secondary_id

K23AA017689

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ZNS-BP

Identifier Type: -

Identifier Source: org_study_id