Pharmacogenetic Prediction of Metoprolol Effectiveness

University of Colorado, Denver462 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

462

Conditions

Hypertension

Interventions

metoprolol succinateDRUG

GenotypingGENETIC

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. Thus the investigator, the subject, and the outcomes investigator will be blind to the intervention.

CYP2D6 PhenotypingPROCEDURE

Phenotype can be discordant from what is predicted by genotype due to variability in absorption, hepatic blood flow, drug interaction and drug elimination. These factors can be accounted for by utilizing a phenotyping assay that determines area under the curve of the probe since the probe is affected by the same variables dictating metabolism phenotype of the therapeutic drug. Investigators will be blind to the patient blood pressure outcome for this intervention.

Eligibility

Sex: ALLMin age: 30 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Subjects between age \>30 years and \< 80 years 2. Subjects have diagnosis of uncontrolled essential hypertension. Exclusion Criteria: 1. end stage liver disease, 2. end stage renal disease, 3. pregnant females, 4. American Society of Anesthesiologists (ASA) classification of \>3, 5. wards of the state, prisoners, 6. decisionally challenged, 7. HR\<60 bpm, 8. AV block\>240 msec, 9. active reactive airway disease, 10. illicit drug abuse in the preceding 30 days, 11. hypersensitivity to metoprolol or its derivatives 12. severe peripheral arterial circulatory disorders. Subjects will have a screening physical exam performed by Dr. Monte prior to enrollment in the study.

Locations (1)

University of Colorado Denver; Emergency Department

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Blood Pressure Decline

Participants with at least a 10% decrease in SBP

Time frame: 4-6 weeks status post initiation

Secondary Outcomes

Heart Rate Decline

10 % decline from pre-initiation heart rate will considered a HR decline success. Number of of participants with at least 10% decline is reported.

Time frame: 4-6 weeks

Adverse Drug Events: CYP2D6 Metabolizer Status

Occurrence of adverse drug events will be captured and stratified by CYP2D6 metabolizer status (Poor Metabolizer (PM), Extensive Metabolizer (EM), Intermediate Metabolizer (IM), and Ultra rapid Metabolizer).

Time frame: 6 weeks

Adverse Drug Events: ADRB1 Genotype

Occurrence of adverse drug events will be captured and stratified by ADRB1 genotype (strong responder, good responder, non-responder).

Time frame: 6 weeks

Data from ClinicalTrials.gov

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