Using multi-omics to predict blood pressure response to medications

Multi-Omics to Predict the Blood Pressure Response to Antihypertensives

This study is testing if certain biological markers can help predict how people with high blood pressure will respond to different blood pressure medications.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Radboud University Medical Center (other)
• Locations: 1 site (Nijmegen)
• Trial ID: NCT05917275 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to develop biomarkers from multiple omics data to predict how patients with primary hypertension will respond to various antihypertensive medications, including olmesartan, amlodipine, and hydrochlorothiazide. Participants will undergo three 4-week treatment periods, during which their blood pressure responses and potential side effects will be monitored. The study seeks to identify specific biomarkers that can forecast both daytime and nighttime blood pressure responses, as well as changes in quality of life associated with treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with grade 1-2 hypertension who are either untreated or on a single antihypertensive medication.

Not a fit: Patients with severe hypertension or those currently on multiple antihypertensive medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized antihypertensive therapies that improve patient outcomes and minimize side effects.

How similar studies have performed: Other studies have shown promise in using omics approaches to personalize treatment, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion criteria

* Age 18 up to and including 75 years
* 24 hours systolic blood pressure 130-164 (corresponding with grade 1-2 hypertension), without the use of blood pressure lowering agents (at screening for patients without pre-treatment or after 4 week wash-out of antihypertensive medication for subjects using a single antihypertensive agent at screening)
* Indication for antihypertensive therapy according to the 2023 European Society of Hypertension Guidelines for the management of arterial hypertension
* Subject is not treated with antihypertensive drugs or is treated with a single antihypertensive drug.
* Female patients must be non-lactating and at no risk of pregnancy for one of the following reasons: 1 year postmenopausal, surgically sterile, or willing to use an acceptable method of contraception (oral contraceptives, approved contraceptive implants, long-term injectable contraception, intrauterine devices, or tubal ligation are allowed.)

Exclusion criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Treatment with 2 or more antihypertensive drugs \< 3 months before inclusion. It is not allowed to stop medication for study purposes in subjects treated with 2 or more anti-hypertensive drugs.
* Known diagnosis of secondary hypertension to an identifiable cause other than treated sleep apnea (e.g., hyperaldosteronism, renal artery stenosis, pheochromocytoma, Cushing's syndrome, coarctation of the aorta, uncontrolled hyper- or hypothyroidism and intracranial tumor)
* Use of VEGF inhibitors, calcineurin inhibitors, glucocorticosteroids, erythropoietin stimulation agents, daily use of NSAID's
* Use of MDMA, methamphetamine, cocaine
* Use of glycyrrhetinic acid containing products , i.e. liquorice, specific herbal teas, \<4 weeks before inclusion. (If patients are willing to stop the intake of glycyrrhetinic acid containing products for the duration of the trial, they can be rescreened after 4 weeks of stopping glycyrrhetinic acid containing products)
* Use of potassium containing supplements
* Concurrent use of medication or a supplement with significant drug interaction with study medication. Special attention is warranted for amlodipine which is metabolized by Cyp3A4. Subjects using strong inhibitors or inducers of Cyp3A4 are excluded from participation in this trial. A list of strong inhibitors and inducers is provided in Addendum 1 of this protocol. For information on possible drug interactions we refer to the website of Lexi-Interact Online (Lexicomp® Drug Interactions - UpToDate (doctorabad.com): https://doctorabad.com/UpToDate/d/di.htm).
* History of myocardial infarction, angina pectoris
* History of atrial fibrillation
* History of severe valvular or structural heart disease (excluding left ventricular hypertrophy)
* History of NYHA class III or IV heart failure or known reduced left ventricular function (ejection fraction (EF) \<30%)
* History of cerebrovascular accident or transient ischemic attack
* History of hypertensive crisis
* History of liver failure
* History of skin cancer
* History of gout
* Current hyperparathyroidism
* Current biliary tract obstruction
* Pregnancy
* Life expectancy \< 1 year
* Known side effect or contra-indication to treatment with calcium channel blockers
* Known side effect or contra-indication to treatment with angiotensin II receptor blockers
* Known side effect or contra-indication to treatment with thiazide diuretics
* Arm circumference \> 46 cm
* Sodium level outside reference range at screening visit
* Potassium level outside reference range at screening visit
* Calcium level outside reference range at screening visit
* eGFR \< 50 ml/min/1,73m2
* Use of loop diuretics.

Where this trial is running

Nijmegen

• Radboudumc — Nijmegen, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Joost Rutten — Radboud University Medical Center
• Study coordinator: Internal Medicine Secretary

Conditions: Primary Hypertension