Zonisamide for Heavy Drinkers With Bipolar Disorder
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Change on Hamilton Depression Rating Scale
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Zonisamide
Subjects will receive zonisamide titrated to a target dose of 500mg orally, daily, double-blind
干预措施: Zonisamide (Drug)
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
干预措施: Placebo (Drug)
结局指标
主要结局
Change on Hamilton Depression Rating Scale
时间窗: 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
时间窗: 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 Total Heavy Drinking Days
时间窗: 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).
次要结局
- 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)
- Change in Number of Heavy Drinking Days Per Week by Time(14 weeks (baseline to endpoint))
- Change in Number of Drinks Per Week by Time(14 weeks (baseline to endpoint))