Utility of Plasma Drug Level Monitoring and CYP2C19 Genotyping in Dose Personalization of Escitalopram
试验速览
- 阶段
- 不适用
- 入组人数
- 148
- 试验地点
- 3
- 主要终点
- Change from Baseline Depression severity score at week 8
研究概览
简要总结
The aims of this study are to:
- Determine the proportion of participants who are underdosed or overdosed under recommended dosing regimen of escitalopram for the depression treatment (10 mg/day)
- Determine and quantify clinical benefits of personalized escitalopram dosing regimen based on the escitalopram blood level monitoring
- Retrospectively estimate whether the information on CYP2C19 genotype is useful in the prediction of escitalopram blood level.
详细描述
Escitalopram is an antidepressant extensively metabolized by the polymorphic CYP2C19 enzyme. Based on CYP2C19 genotype, patients can be classified either as:
- Normal metabolizers (Normal CYP2C19 enzyme capacity)
- Intermediate metabolizers (Decreased CYP2C19 enzyme capacity)
- Poor metabolizers (Absent CYP2C19 enzyme capacity)
- Ultra rapid metabolizers (Increased CYP2C19 enzyme capacity)
Adequate escitalopram exposure is needed to achieve optimal clinical response in the treatment of depression: too low drug plasma levels can lead to the lack of pharmacological effect, whereas too high drug plasma levels increases the incidence of adverse effects. There is evidence that patients with variant CYP2C19 genotypes have abnormal escitalopram exposure and could benefit from escitalopram dose personalization, but precise evidence-based protocol for personalized dosing of escitalopram has not been developed yet. This multicentric observational clinical trial is designed to collect crucial information for the development of such protocol that will be based on drug plasma level monitoring and/or CYP2C19 genotyping.
The course of the study will be as follows:
Initial Visit (V0):
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed Major Depressive Disorder
- •Starting monotherapy with escitalopram
- •Signed written informed consent
排除标准
- •Patient's requests to leave the study
- •Patients who had taken escitalopram before
- •Severe liver function impairment (abnormal AST/ALT ratio)
- •Severe kidney function impairment (abnormal creatinine clearance)
- •History of drug addiction (sporadic use is permitted)
- •Suicide risk
- •Patients who are taking strong CYP2C19 inhibitors
- •Severe adverse drug reaction
研究组 & 干预措施
Standard dose
Patients are allocated to this group at visit V1 if 10 mg/day escitalopram treatment resulted in optimal escitalopram exposure (25-50 ng/ml) as measured at VK. These patients will continue their treatment with 10 mg/day during the V1-V2 period.
干预措施: Escitalopram (Drug)
Adjusted dose
Patients are allocated to this group at visit V1 if 10 mg/day escitalopram dose resulted in to high (>50 ng/ml) or to low (<25 ng/ml) escitalopram exposure, as measured at VK. These patients will be treated with the adjusted escitalopram dose, different from 10 mg/day, during the V1-V2 period.
干预措施: Escitalopram (Drug)
结局指标
主要结局
Change from Baseline Depression severity score at week 8
时间窗: 8 Weeks
Measured with clinician reported 21-item Hamilton rating scale for depression (HAM-D). Scale gives a score from 0 to 52 where higher score represents higher depression severity and worse outcome.
Adverse drug reaction severity score at week 8
时间窗: 8 Weeks
Measured with clinician reported UKU (Udvalg for Kliniske Undersogelser) side effect rating scale. Scale gives summary score from 0 to 3 where higher scores correspond to the greater side-effects severity and worse outcome.
次要结局
- Retrospectively determined regression formula for prediction of escitalopram plasma levels at Vk based on CYP2C19 metabolizer status(8 Weeks)
- Change from Baseline Depression severity score at week 4(4 Weeks)
- Adverse drug reaction severity score at week 4(4 Weeks)
- Number of participants with escitalopram plasma concentrations outside the therapeutic window(at Week 2)
研究者
Marin Jukic
Assistant Professor, PhD
University of Belgrade