NCT07490067

Mechanistic Clinical Trial Comparing the Pharmacokinetics/Pharmacodynamics of Metoprolol in Heart Failure With Reduced Ejection Fraction Patients With Low vs. High Polygenic Score

Personalizing Heart Failure Treatment With Genomics: A Clinical Trial to Understand the Mechanisms and Validate a Polygenic Risk Score for Beta-Blocker Response

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: University of Michigan · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this trial is to better understand how the beta-blocker metoprolol works in people with Heart Failure with Reduced Ejection Fraction (HFrEF) according to participants genetics. Participants will have the beta-blocker (BB) polygenic score calculated from genotype data. The score will be used to stratify the patients in the low and high polygenic score groups in the study. The hypotheses for this trial are: * HFrEF patients with high polygenic score will have weaker cardiovascular responses to metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score have lower steady-state plasma concentrations of metoprolol succinate than HFrEF patients with low polygenic score. * HFrEF patients with high polygenic score require higher metoprolol succinate plasma concentrations to achieve similar cardiovascular effects as those with low polygenic score.

Conditions

• Heart Failure With Reduced Ejection Fraction

Interventions

Type	Name	Description
DRUG	Metoprolol Succinate	Participants will be given daily metoprolol and the dose will be titrated up to 200 milligrams daily (over 6-12 weeks) or the maximum tolerated dose. Once this dose is reached treatment will continue for approximately 5-8 months. In addition, participants, will have various visits that include laboratory and cardiac testing at certain time points.
DEVICE	Beta-Blocker Polygenic Score	The purpose of the beta-blocker polygenic score is to predict which HFrEF patients will respond better to beta-blocker therapy. It will be used to stratify the patients in the low and high polygenic score groups in the study. There are no post-manufacturing modifications to the score.
DEVICE	Illumina Infinium Global Diversity Array with Enhanced Pharmacogenomics (PGx)	If the participant does not already have genotype data available through Michigan Genomics Initiative (MGI), then this device will be used to genotype DNA sample, which will be used to calculate the polygenic score. There are no post-manufacturing modifications to the device.

Timeline

• Start date: 2026-04-01
• Primary completion: 2029-07-01
• Completion: 2029-07-01
• First posted: 2026-03-24
• Last updated: 2026-04-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study