Pharmacogenetic Prediction of Metoprolol Effectiveness
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 462
- 试验地点
- 1
- 主要终点
- Blood Pressure Decline
研究概览
简要总结
The investigators will prospectively follow a population of patients with uncontrolled high blood pressure beginning metoprolol succinate therapy to determine the drug effect in an observational clinical trial. The investigators will determine each individual's genotype for both CYP2D6 and Adrenoceptor Beta 1 (ADRB1). Metabolomic markers will be identified to determine if specific metabolites are associated with drug response. The investigators' overall objective is to determine if genetics predicts metoprolol succinate response better than clinical factors such as age, race, body mass index, dose, and medication co-ingestion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects between age >30 years and < 80 years
- •Subjects have diagnosis of uncontrolled essential hypertension.
排除标准
- •end stage liver disease,
- •end stage renal disease,
- •pregnant females,
- •American Society of Anesthesiologists (ASA) classification of >3,
- •wards of the state, prisoners,
- •decisionally challenged,
- •HR<60 bpm,
- •AV block>240 msec,
- •active reactive airway disease,
- •illicit drug abuse in the preceding 30 days,
- •hypersensitivity to metoprolol or its derivatives
- •severe peripheral arterial circulatory disorders.
- •Subjects will have a screening physical exam performed by Dr. Monte prior to enrollment in the study.
研究组 & 干预措施
Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping
The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors.
metoprolol succinate
Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete.
CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
干预措施: metoprolol succinate (Drug)
Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping
The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors.
metoprolol succinate
Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete.
CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
干预措施: Genotyping (Genetic)
Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping
The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors.
metoprolol succinate
Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete.
CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
干预措施: CYP2D6 Phenotyping (Procedure)
结局指标
主要结局
Blood Pressure Decline
时间窗: 4-6 weeks status post initiation
Participants with at least a 10% decrease in SBP
次要结局
- Adverse Drug Events: CYP2D6 Metabolizer Status(6 weeks)
- Heart Rate Decline(4-6 weeks)
- Adverse Drug Events: ADRB1 Genotype(6 weeks)