Zonisamide for Heavy Drinkers With Bipolar Disorder

NCT01566370 | Terminated Phase 2 Results DMC

• 3 other identifiers: ZNS-BPVACT MIRECCK23AA017689
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 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.

Conditions

Alcohol Use Disorders; Bipolar Disorder

Keywords

alcoholism; alcohol use disorder; alcohol dependence; alcohol abuse; bipolar; anticonvulsant; zonisamide

Outcome Measures

Primary Outcomes (3)

• 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).

  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

  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

  14 weeks

Secondary Outcomes (7)

• Percentage of Abstinent Days

  over four weeks, from week 11 through 14

• Change in Alcohol Urge Questionnaire Score

  from baseline to endpoint, 14 weeks

• Change in Gamma Glutamyl Transferase (GGT)

  14 weeks

• Change in Beck Depression Inventory (BDI) Scores

  14 weeks

• Percentage of Total Drinking Days

  4 weeks

Study Arms (2)

Zonisamide

EXPERIMENTAL

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

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

Drug: Placebo

Interventions

Zonisamide DRUG

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

Also known as: Zonegran

Zonisamide

Placebo DRUG

placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

VA Connecticut Healthcare System

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Alcoholism; Bipolar Disorder

Interventions

Zonisamide

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Bipolar and Related Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Albert Arias
• Organization: Yale/VA Connecticut Healthcare system

albert.arias@va.gov

2039325711

Study Officials

• Albert J Arias, MD

  Yale University, VA CT Health System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: March 29, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: January 13, 2017
• Results First Posted: April 22, 2016

Record last verified: 2016-11

Locations

US (1)