HT-PREDICT: Multi-Omics to Predict the Blood Pressure Response to Antihypertensives

Sponsor

Radboud University Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05917275

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Hypertension	Drug: Amlodipine Drug: Olmesartan Drug: Hydrochlorothiazide Drug: Amlodipine/Olmesartan	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Diagnostic

Official Title:

Multi-Omics to Predict the Blood Pressure Response to Antihypertensives

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 4 weeks of Amlodipine	Drug: Amlodipine 4 weeks of Amlodipine
Experimental: 4 weeks of Olmesartan	Drug: Olmesartan 4 weeks of Olmesartan
Experimental: 4 weeks of Hydrochlorothiazide	Drug: Hydrochlorothiazide 4 weeks of Hydrochlorothiazide
Experimental: 4 weeks of Amlodipine/Olmesartan	Drug: Amlodipine/Olmesartan 4 weeks of Amlodipine/Olmesartan

Outcome Measures

Primary Outcome Measures

Predictive value of Multi-Omics profile for blood pressure [4 weeks after start treatment]
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).

Secondary Outcome Measures

Predictive value of Multi-Omics profile for night-time blood pressure [4 weeks after start treatment]
Predictive value of a MOMICs profile to discriminate subjects with a decrease in night-time 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).
Correlation Multi-Omics profile and adverse effects [correlation between changes from baseline to 4 weeks after start treatment]
Correlation between changes in individual biomarkers and adverse effects as documented using adverse effects questionnaire and SF-36

Other Outcome Measures

Changes in Multi-Omics profile after treatment [4 weeks after start treatment]
Change in individual Multi-Omics profile components after treatment with olmesartan, amlodipine and hydrochlorothiazide compared with biomarkers levels at baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-75 years
24 hours systolic blood pressure 130-164 mmHg, without the use of blood pressure lowering agents (at screening for patients without pretreatment or after 4 week wash-out of antihypertensive medication)
Indication for antihypertensive therapy according to the treating physician
Female subjects of childbearing potential must be 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:

Treatment with 2 or more anti-hypertensive drugs < 3 months before inclusion. 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 supplements with significant drug interaction with study medication, for example carbamazepine (interaction with amlodipine through induction of CYP3A4)*
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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Radboud University Medical Center

Investigators

Principal Investigator: Joost Rutten, Radboud University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Radboud University Medical Center

ClinicalTrials.gov Identifier:

NCT05917275

Other Study ID Numbers:

114516
2023-505239-10-00

First Posted:

Jun 23, 2023

Last Update Posted:

Jun 23, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Essential Hypertension

Study Results

No Results Posted as of Jun 23, 2023