A Double-Blind Randomized Placebo Controlled Study of Quetiapine for the Treatment of Depression in Adolescents With Bipolar Disorder
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Children's Depression Rating Scale (CDRS): Measure of efficacy will be a change in CDRS total scores from baseline endpoint.
研究概览
简要总结
In this study, quetiapine is being tested for the possible treatment of bipolar I disorder with an acute depressive episode in children and adolescents.
We hypothesize that quetiapine will be more efficacious than placebo for the treatment of episodes of major depression associated with adolescent BP. Moreover, we hypothesize that quetiapine will be safe and well-tolerated compared with placebo for the treatment of depression associated with adolescent BP. Based on data from the BOLDER study and other studies of atypical antipsychotics in patients with bipolar depression (Calabrese et al., 2004, Macfadden et al., 2004, Tohen et al., 2004), which in general reveal effect sizes of approximately 0.5, a conservative sample size calculation, assuming power of .8, estimates we would need approximately 15 patients in each group to identify a statistically significant group difference in our main outcome measure, change form baseline to endpoint in the Children's Depression Rating Scale (Poznanski, 1979).
详细描述
This is a double-blind, randomized 56-day treatment trial of quetiapine vs. placebo for the treatment of bipolar adolescents with acute depression. Randomization will be stratified by sex, the presence of psychotic features, and a site specific randomization schedule will be determined. Stratification of randomization by sex is necessary to control for the higher rate of co-occurring ADHD in males than in females with bipolar disorder. Bipolar disorder with ADHD may be more treatment refractory than bipolar disorder without ADHD. Stratification by the presence of psychosis is necessary to avoid all patients with psychosis being assigned to one treatment group. A randomization schedule will be developed by the Children's Hospital Medical Center Investigational Pharmacy.
Procedures Thirty adolescents who are hospitalized for an episode of major depression associated with BP, type I, (ages 12-18) will be recruited for the study over two years.
After providing informed consent (the parent or legal guardian), informed assent (the child), and signing the document (both the parent and the child), subjects will be evaluated using the Washington University at St. Louis Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS, Geller et al., 1998) by raters with extensive training in the instrument and established inter-rater reliability (ICC>0.9) (DelBello et al., 2004). The WASH-U K-SADS is a semi-structured clinical interview with established validity and reliability to assess the presence of DSM-IV Axis I psychiatric disorders in children and adolescents (Geller et al., 1998). The K-SADS involves an interview with the child and another interview with the parent.
If the diagnosis of bipolar disorder, type I, current episode depressed is confirmed by the K-SADS, the following scales will also be performed:
- The Children's Depression Rating Scale (CDRS) to assess the severity of depressive symptoms (Poznanski et al., 1979);
- The Young Mania Scale (YMRS) to assess the severity of manic symptoms (Fristad et al., 1992; Young et al., 1978);
- The Hamilton Anxiety Rating Scale (HAM-A) to assess the severity of anxiety symptoms (Hamilton, 1959)
- The Clinical Global Impression Scale BP Version (CGI-BP) to quantify the child's overall baseline functioning (National Institute of Mental health, 1985); The CGI-BP is used by the clinician to record the severity of illness at the time of assessment. The score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). At all visits following baseline, we will also perform the CGI-BP Improvement Scale to quantify the change from baseline in overall functioning. The score ranges from 1 (very much improved) to 7 (very much worse).
- The Simpson-Angus Scale (Simpson and Angus, 1970), Barnes Akathisia Scale (Barnes 1989) and Abnormal Involuntary Movement Scale (AIMS, US Department of Health, 1976) to assess for extrapyramidal symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 12 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be included in this study, subjects must meet the following criteria:
- •Male or female patients, 12-18 years of age.
- •Female patients of menarche must be using a medically accepted means of contraception (e.g. oral contraceptives, Depo-Provera, abstinence).
- •Each patient's authorized legal guardian must understand the nature of the study and must provide written informed consent. Each patient must also give assent to study participation.
- •Patients must have a diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) BP, type I and currently display an acute depressive episode as determined by K-SADS (Geller et al 2000).
- •Patients must have a baseline (day 0) CDRS score of at least
- •Subjects should be fluent in English.
排除标准
- •Patients will be excluded from the protocol for any of the following reasons:
- •Female patients who are either pregnant or lactating.
- •Clinically significant or unstable hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions.
- •Any history of current or past diabetes that was treated with pharmacological intervention.
- •Neurological disorders including epilepsy, stroke, or severe head trauma.
- •Clinically significant laboratory abnormalities, on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, thyroid indices and EKG.
- •Depression due to a general medical condition or substance-induced depression (DSM-IV).
- •Mental retardation (IQ <70).
- •YMRS score of >
- •History of hypersensitivity to or intolerance of quetiapine.
- •Prior history of quetiapine non-response.
- •DSM-IV substance (except nicotine or caffeine) dependence within the past 3 months.
- •Judged clinically to be at suicidal risk (defined as having active suicidal ideation, intent or plan, or a serious suicide attempt within 30 days, or a baseline CDRS suicide score of > 3).
- •Participation in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry.
- •Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day
- •Treatment with concurrent mood stabilizers or anticonvulsants, benzodiazepines (except as described below), psychostimulants, guanethidine, or guanadrel, or antidepressants.
- •Patient who were treated with carbamazepine at any point during the month prior to screening.
- •Schizophrenia or other psychotic disorders (including schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified) as defined in the DSM-IV.
- •Major depressive disorder, dysthymic disorder, depressive disorder not otherwise specified.
- •Subjects who are not fluent in English.
结局指标
主要结局
Children's Depression Rating Scale (CDRS): Measure of efficacy will be a change in CDRS total scores from baseline endpoint.
次要结局
- Secondary Efficacy Measures
- Safety
- Hamilton Anxiety Rating Scale (HAM-A): Measure of efficacy will be change from baseline to endpoint in HAM-A
- Incidence of adverse events
- CDRS response rate: Defined by a > 50% decrease from baseline to endpoint in CDRS total score.
- Clinical Global Impression Improvement Scale BP Version (CGI-I BP) Improvement Score response rate: Defined by an endpoint CGI-I score of 1 or 2 (much or very much improved)
- Change from baseline to endpoint in all laboratory measures and vital signs.
- Proportion of patients who met criteria for treatment-emergent mania (YMRS score > 16 on two consecutive visits or at final assessment).
- Incidence of EPS (as measured by change from baseline to endpoint in EPS rating scales)
研究者
Melissa Delbello
Professor
University of Cincinnati