Zonisamide for Heavy Drinkers With Bipolar Disorder (ZNSBP)
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.
|Alcohol Use Disorders Bipolar Disorder||Drug: Zonisamide Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Zonisamide for Heavy Drinkers With Bipolar Disorder|
- 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
- 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.
- 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
- 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
- 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
- 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.
- 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
- 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
|Study Start Date:||May 2012|
|Study Completion Date:||July 2013|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01566370
|United States, Connecticut|
|VA Connecticut Healthcare System|
|West Haven, Connecticut, United States, 06516|
|Principal Investigator:||Albert J Arias, MD||Yale University, VA CT Health System|