Multi-Omics to Predict the Blood Pressure Response to Antihypertensives

NCT05917275 | Recruiting Phase 4

• 2 other identifiers: 1145162023-505239-10-00
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to develop biomarkers composed of multiple OMICs (MOMICs) for prediction of blood pressure response to antihypertensive drugs in the treatment of primary hypertension. The main objectives are:

• Primary objective: \- To identify MOMICs biomarkers that predict the response in 24-hour blood pressure to antihypertensive treatment for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine)
• Secondary objectives:
• To identify a MOMICs biomarker that predict the response in night-time blood pressure to anti-hypertensive treatment for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine)
• To identify MOMICs biomarkers that predict side effects, including changes in QoLof olmesartan, amlodipine and hydrochlorothiazide.
• Exploratory objective:
• To assess changes in MOMICs biomarkers induced by each drug Participants will undergo three 4-week treatment periods:
• Each subject receives 3 out of 4 possible treatments (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine).
• Before and after each treatment period OMICS measurements and an ABPM are performed.
• At the end of each treatment period blood is sampled for drug level testing to assess adherence.
• Electrolytes and kidney function are checked 5-7 days after start of each treatment period.

Conditions

Primary Hypertension

Outcome Measures

Primary Outcomes (1)

• Predictive value of Multi-Omics profile for blood pressure

  Predictive value of a MOMICs profile to discriminate subjects with a decrease in 24-hour blood pressure below the median from subjects with a decrease in 24-hour blood pressure above the median for each treatment group (olmesartan, amlodipine, hydrochlorothiazide, olmesartan/amlodipine).

  4 weeks after start treatment

Secondary Outcomes (2)

• Predictive value of Multi-Omics profile for night-time blood pressure

  4 weeks after start treatment

• Correlation Multi-Omics profile and adverse effects

  correlation between changes from baseline to 4 weeks after start treatment

Other Outcomes (1)

• Changes in Multi-Omics profile after treatment

  4 weeks after start treatment

Study Arms (4)

4 weeks of Amlodipine

EXPERIMENTAL

Drug: Amlodipine

4 weeks of Olmesartan

EXPERIMENTAL

Drug: Olmesartan

4 weeks of Hydrochlorothiazide

EXPERIMENTAL

Drug: Hydrochlorothiazide

4 weeks of Amlodipine/Olmesartan

EXPERIMENTAL

Drug: Amlodipine/Olmesartan

Interventions

Amlodipine DRUG

4 weeks of Amlodipine

4 weeks of Amlodipine

Olmesartan DRUG

4 weeks of Olmesartan

4 weeks of Olmesartan

Hydrochlorothiazide DRUG

4 weeks of Hydrochlorothiazide

4 weeks of Hydrochlorothiazide

Amlodipine/Olmesartan DRUG

4 weeks of Amlodipine/Olmesartan

4 weeks of Amlodipine/Olmesartan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 up to and including 75 years
• 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.)

You may not qualify if:

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

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, Netherlands

RECRUITING

MeSH Terms

Conditions

Essential Hypertension

Interventions

Amlodipine; olmesartan; Hydrochlorothiazide; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Olmesartan Medoxomil; Imidazoles; Azoles; Tetrazoles; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Joost Rutten

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Internal Medicine Secretary

CONTACT

+31243618819; secretariaatstaf.aig@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 23, 2023
• Study Start: April 4, 2024
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: June 10, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)