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

Primary Purpose

Primary Hypertension

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Amlodipine
Olmesartan
Hydrochlorothiazide
Amlodipine/Olmesartan
Sponsored by
Radboud University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Primary Hypertension

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    4 weeks of Amlodipine

    4 weeks of Olmesartan

    4 weeks of Hydrochlorothiazide

    4 weeks of Amlodipine/Olmesartan

    Arm Description

    Outcomes

    Primary Outcome Measures

    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).

    Secondary Outcome Measures

    Predictive value of Multi-Omics profile for night-time blood pressure
    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 in individual biomarkers and adverse effects as documented using adverse effects questionnaire and SF-36

    Full Information

    First Posted
    June 6, 2023
    Last Updated
    September 5, 2023
    Sponsor
    Radboud University Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05917275
    Brief Title
    Multi-Omics to Predict the Blood Pressure Response to Antihypertensives
    Acronym
    HT-PREDICT
    Official Title
    Multi-Omics to Predict the Blood Pressure Response to Antihypertensives
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    October 2025 (Anticipated)
    Study Completion Date
    October 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Radboud University Medical Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Primary Hypertension

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 4
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    96 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    4 weeks of Amlodipine
    Arm Type
    Experimental
    Arm Title
    4 weeks of Olmesartan
    Arm Type
    Experimental
    Arm Title
    4 weeks of Hydrochlorothiazide
    Arm Type
    Experimental
    Arm Title
    4 weeks of Amlodipine/Olmesartan
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Amlodipine
    Intervention Description
    4 weeks of Amlodipine
    Intervention Type
    Drug
    Intervention Name(s)
    Olmesartan
    Intervention Description
    4 weeks of Olmesartan
    Intervention Type
    Drug
    Intervention Name(s)
    Hydrochlorothiazide
    Intervention Description
    4 weeks of Hydrochlorothiazide
    Intervention Type
    Drug
    Intervention Name(s)
    Amlodipine/Olmesartan
    Intervention Description
    4 weeks of Amlodipine/Olmesartan
    Primary Outcome Measure Information:
    Title
    Predictive value of Multi-Omics profile for blood pressure
    Description
    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).
    Time Frame
    4 weeks after start treatment
    Secondary Outcome Measure Information:
    Title
    Predictive value of Multi-Omics profile for night-time blood pressure
    Description
    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).
    Time Frame
    4 weeks after start treatment
    Title
    Correlation Multi-Omics profile and adverse effects
    Description
    Correlation between changes in individual biomarkers and adverse effects as documented using adverse effects questionnaire and SF-36
    Time Frame
    correlation between changes from baseline to 4 weeks after start treatment
    Other Pre-specified Outcome Measures:
    Title
    Changes in Multi-Omics profile after treatment
    Description
    Change in individual Multi-Omics profile components after treatment with olmesartan, amlodipine and hydrochlorothiazide compared with biomarkers levels at baseline.
    Time Frame
    4 weeks after start treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Internal Medicine Secretary
    Phone
    +31243618819
    Email
    secretariaatstaf.aig@radboudumc.nl
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Joost Rutten
    Organizational Affiliation
    Radboud University Medical Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Multi-Omics to Predict the Blood Pressure Response to Antihypertensives

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