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| ID | Type | Description | Link |
|---|---|---|---|
| 1K23GM110516-01 | U.S. NIH Grant/Contract | View source |
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Study was terminated due to the change in funding.
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| Name | Class |
|---|---|
| National Institute of General Medical Sciences (NIGMS) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| metoprolol succinate | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Pressure Decline | Participants with at least a 10% decrease in SBP | 4-6 weeks status post initiation |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Adverse Drug Events: CYP2D6 Metabolizer Status |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
Exclusion Criteria:
Subjects will have a screening physical exam performed by Dr. Monte prior to enrollment in the study.
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| Name | Affiliation | Role |
|---|---|---|
| Andrew Monte, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Denver; Emergency Department | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32160915 | Derived | Brocker CN, Velenosi T, Flaten HK, McWilliams G, McDaniel K, Shelton SK, Saben J, Krausz KW, Gonzalez FJ, Monte AA. Metabolomic profiling of metoprolol hypertension treatment reveals altered gut microbiota-derived urinary metabolites. Hum Genomics. 2020 Mar 11;14(1):10. doi: 10.1186/s40246-020-00260-w. |
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322 participants screen failed or withdrew after consent, but prior to starting the study & receiving the intervention
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| ID | Title | Description |
|---|---|---|
| FG000 | Metoprolol Succinate, Genotyping, Clinical Factors, and 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Metoprolol Succinate, Genotyping, Clinical Factors, and 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood Pressure Decline | Participants with at least a 10% decrease in SBP | Posted | Count of Participants | Participants | 4-6 weeks status post initiation |
|
6 Weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metoprolol Succinate, Genotyping, Clinical Factors, and 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Andrew Monte, MD, PhD | University of Colorado Denver | Anschutz | 3037241111 | clinicalresearchsupportcenter@ucdenver.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 2, 2015 | Aug 18, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D008790 | Metoprolol |
| D005838 | Genotype |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Genotyping |
| Genetic |
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 Phenotyping | Procedure | 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. |
|
|
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 |
| 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 |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 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. | Posted | Count of Participants | Participants | 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). | Posted | Number | participants with events | 6 weeks |
|
|
|
| Other Pre-specified | Metabolomic Factors | The top 5 metabolomic factors associated with SBP decline will be captured and stratified by CYP2D6 genotype and phenotype groups. | Not Posted | 0-6 weeks | Participants |
| 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). | Posted | Number | participants with events | 6 weeks |
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| 0 |
| 140 |
| 0 |
| 140 |
| 0 |
| 140 |
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| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D055614 | Genetic Phenomena |
| Title | Measurements |
|---|---|
|