Study Stopped
Study was terminated due to the change in funding.
Pharmacogenetic Prediction of Metoprolol Effectiveness
2 other identifiers
interventional
462
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable hypertension
Started Sep 2014
Typical duration for not_applicable hypertension
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2014
CompletedFirst Submitted
Initial submission to the registry
November 13, 2014
CompletedFirst Posted
Study publicly available on registry
November 18, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 23, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 23, 2017
CompletedResults Posted
Study results publicly available
September 16, 2021
CompletedSeptember 16, 2021
August 1, 2021
3 years
November 13, 2014
August 18, 2021
August 18, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Blood Pressure Decline
Participants with at least a 10% decrease in SBP
4-6 weeks status post initiation
Secondary Outcomes (3)
Heart Rate Decline
4-6 weeks
Adverse Drug Events: CYP2D6 Metabolizer Status
6 weeks
Adverse Drug Events: ADRB1 Genotype
6 weeks
Other Outcomes (1)
Metabolomic Factors
0-6 weeks
Study Arms (1)
Metoprolol succinate, CYP2D6 Genotyping, CYP2D6 Phenotyping
EXPERIMENTALThe 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.
Interventions
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.
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 Criteria
You may qualify if:
- Subjects between age \>30 years and \< 80 years
- Subjects have diagnosis of uncontrolled essential hypertension.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Colorado Denver; Emergency Department
Aurora, Colorado, 80045, United States
Related Publications (1)
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.
PMID: 32160915DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Andrew Monte, MD, PhD
- Organization
- University of Colorado Denver | Anschutz
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew Monte, MD
University of Colorado, Denver
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 13, 2014
First Posted
November 18, 2014
Study Start
September 1, 2014
Primary Completion
August 23, 2017
Study Completion
August 23, 2017
Last Updated
September 16, 2021
Results First Posted
September 16, 2021
Record last verified: 2021-08