An interventional study of metoprolol succinate and Genotyping in Hypertension, sponsored by University of Colorado, Denver. Terminated at 1 site in United States. Open to participants aged 30 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-09-16.
Sponsored by University of Colorado, Denver · Not applicable, Interventional, and Treatment
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.
6,689 studies on the registry are indexed under Hypertension; 965 are open to participants now.
This study's enrollment of 462 is above the median of 90 across 4,995 interventional studies indexed under Hypertension.
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Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.
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Exclusion Criteria:
Subjects will have a screening physical exam performed by Dr. Monte prior to enrollment in the study.
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.
Drug: metoprolol succinate · Genetic: Genotyping · Procedure: CYP2D6 Phenotyping
Also known as: Lopressor
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.
Also known as: CYP2D6 genotyping and ADRB1 genotyping
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.
Also known as: Dextromethorphan probe of CYP2D6
Blood Pressure Decline
Participants with at least a 10% decrease in SBP
Time frame: 4-6 weeks status post initiation
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
Metabolomic Factors
The top 5 metabolomic factors associated with SBP decline will be captured and stratified by CYP2D6 genotype and phenotype groups.
Time frame: 0-6 weeks
| Milestone | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| Started | 140 |
| Completed | 140 |
| Not completed | 0 |
Participants with at least a 10% decrease in SBP
| Participants | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| Blood Pressure Decline | 85 |
10 % decline from pre-initiation heart rate will considered a HR decline success. Number of of participants with at least 10% decline is reported.
| Participants | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| Heart Rate Decline | 67 |
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).
| participants with events | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| CYP2D6 metabolizer status: EM | 3 |
| Other Metabolizer Statuses | 0 |
The top 5 metabolomic factors associated with SBP decline will be captured and stratified by CYP2D6 genotype and phenotype groups.
Results for this outcome have not been posted.
Occurrence of adverse drug events will be captured and stratified by ADRB1 genotype (strong responder, good responder, non-responder).
| participants with events | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| ADRB1 genotype: Strong Responder | 1 |
| ADRB1 genotype: Good Responder | 2 |
| ADRB1 genotype: Non-responder | 0 |
Collected over 6 Weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping | 0/140 (0%) | 0/140 (0%) | 0/140 (0%) |
| Age, Continuous(years) | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| Mean | 52.12 ± 11.05 |
| Sex: Female, Male(Participants) | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| Female | 55 |
| Male | 85 |
| Ethnicity (NIH/OMB)(Participants) | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| Hispanic or Latino | 24 |
| Not Hispanic or Latino | 116 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| American Indian or Alaska Native | 1 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 60 |
| White | 70 |
| More than one race | 6 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping |
|---|---|
| United States | 140 |
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University of Colorado, Denver