Pharmacogenetic Prediction of Metoprolol Effectiveness

Hypertension Clinical Trial

Official title:

Pharmacogenetic Prediction of Metoprolol Effectiveness

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02293096
• Other study ID #: 13-3174
• Secondary ID: 1K23GM110516-01
• Status: Terminated
• Phase: N/A
• Start date: September 2014
• Est. completion date: August 23, 2017

Study information

• Verified date: August 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 462
• Est. completion date: August 23, 2017
• Est. primary completion date: August 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• metoprolol succinate

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

Procedure:
• CYP2D6 Phenotyping
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.

Locations

Country	Name	City	State
United States	University of Colorado Denver; Emergency Department	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of General Medical Sciences (NIGMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Metabolomic Factors	The top 5 metabolomic factors associated with SBP decline will be captured and stratified by CYP2D6 genotype and phenotype groups.	0-6 weeks
Primary	Blood Pressure Decline	Participants with at least a 10% decrease in SBP	4-6 weeks status post initiation
Secondary	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.	4-6 weeks
Secondary	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).	6 weeks
Secondary	Adverse Drug Events: ADRB1 Genotype	Occurrence of adverse drug events will be captured and stratified by ADRB1 genotype (strong responder, good responder, non-responder).	6 weeks