Topiramate in Treatment Refractory Psychotic Illness: Effects on Weight Gain and Psychopathology
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Weight loss
研究概览
简要总结
Clozapine is the sole AP agent with superiority in treatment refractory schizophrenia, but it also is associated with the greatest risk of weight gain and other metabolic abnormalities. Topiramate, an anticonvulsant agent, possesses a weight-reducing effect. Furthermore, some studies have suggested that Topiramate may be associated with improvements in psychopathology in treatment refractory schizophrenia. Here the investigators propose to determine the role of topiramate for augmentation purposes (psychopathology) and as an adjunctive pharmacological intervention for weight loss in overweight/obese individuals with Ultra-Treatment Resistant Schizophrenia or Schizoaffective disorder taking clozapine.
详细描述
Schizophrenia is a chronic illness characterized by social and vocational disruptive functioning. While >70% of individuals with first episode illness respond to antipsychotics (APs), there remains a subgroup left with persisting psychotic symptoms. For these individuals, clozapine (CLZ) is also the sole drug with treatment superiority, but also carries the greatest metabolic liability. Another complicating factor in those treated with CLZ is the observation that while effective in some, 40-70% of individuals fail to show significant improvement with CLZ, often leading to augmentation strategies. While controlled trials are, in general lacking, a number of agents have been suggested as useful. One such group of medications includes the anticonvulsants.
Topiramate represents one of the newer anticonvulsant agents approved for the treatment of epilepsy and prophylaxis of migraines. Importantly, topiramate possesses a weight-reducing effect that has been substantiated by a meta-analysis in non-psychiatric patients. Interestingly, topiramate has been studied as an adjunctive therapy in treatment-resistant schizophrenia with some evidence demonstrating small to moderate benefits with topiramate augmentation on psychopathology. However, these benefits must also be weighed against reports (primarily from epilepsy populations), that topiramate may cause cognitive dysfunction.
This study will examine:
- Topiramate-related effects on weight
- Topiramate-related effects on glucose tolerance and insulin sensitivity
- Topiramate-related effects on psychopathology and cognition
- Topiramate-related effects on adiposity
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
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 17 Years 至 59 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Schizophrenia or Schizoaffective disorder
- •17-59 years of age
- •Clozapine treatment for at least 12 weeks at a dose 350 mg/d or greater and/or plasma clozapine levels of 300 ng/mL or greater
- •CGI must be 4 or higher and/or GAF < 50
- •BMI greater than or equal to 25
排除标准
- •Alcohol use disorder
- •Patients with liver, or renal dysfunction
- •Females of child bearing age not on a regular contraceptive, females who are nursing
- •Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematological, or pulmonary disease.
- •HbA1c > 9%, or symptomatic hyperglycemia with metabolic decompensation
- •Prior lack of efficacy or tolerability of Topiramate
- •Addition of new hypoglycemic or lipid lowering medication within 2 months of starting study
- •Patients treated with Valproic Acid
- •Patients treated with hydrochlorothiazide
- •Switch in antipsychotic medications within 3 months of study entry
- •Major medical or surgical event within the preceding 3 months
- •History of renal stones
- •Use of Carbonic Anhydrase Inhibitor
- •History of glaucoma
- •Acute Suicidal risk
研究组 & 干预措施
Placebo
Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit.
干预措施: Placebo (Other)
Topiramate
Topiramate will be dispensed on a biweekly basis, and pill counts conducted at each visit.
干预措施: Topiramate (Drug)
结局指标
主要结局
Weight loss
时间窗: 16 weeks
Measured in pounds
次要结局
- Psychopathology - Clinical Global Impression (CGI)(16 weeks)
- Psychopathology - Global Assessment of Functioning (GAF)(16 weeks)
- Psychopathology - Brief Psychiatric Rating Scale (BPRS)(16 weeks)
- Insulin sensitivity(16 weeks)
- Psychopathology - Positive and Negative Syndrome Scale (PANSS)(16 weeks)
- Glucose Tolerance(16 weeks)
研究者
Margaret Hahn
Clinician-Scientist
Centre for Addiction and Mental Health