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HypertensionNCT06175663

Hyperintense: Midlife Hypertension and the Brain

An observational study of Hypertension and Small Vessel Cerebrovascular Disease, run by Radboud University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Cerebral small vessel disease (SVD) describes a set of pathologies affecting the smallest blood vessels in the brain. SVD contributes to up to a fifth of ischemic and hemorrhagic strokes en is the main vascular cause of dementia. Read more about this study

Who is it for?
Ages 18 to 55 years
What is being tested?
Antihypertensive medication withdrawal
How many people
130 participants
Where
1 siteNetherlands
Study dates
6 Jul 2021to 31 Dec 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Study population: Patients will be recruited through the outpatient clinic of the Department of Internal Medicine of the Radboudumc and Rijnstate hospital, where they are referred to for their high blood pressure.

Who may be able to join

  • Age 18-40 years
  • Blood pressure above 140/90 mmHg, measured within three months prior to study participation
  • Age 18-55 years
  • Undergoing diagnostic routine of temporary antihypertensive withdrawal for biochemical analysis as part of clinical work-up

Who cannot join

  • Pre-existing cerebrovascular disease
  • Pregnancy
  • Contraindications for 3 T MRI
  • Renal function eGFR below 30 ml/min (for Dynamic Contrast Enhanced [DCE]-MRI
  • Major risk factors for acute ischemic stroke other than SVD according to the TOAST criteria, including, but not limited to, large-artery atherosclerosis, cardioembolism and vasculitis based on medical history and ultrasound of the carotids collected at baseline or any chronic disease that could lead to brain lesions mimicking SVD
  • Major (neurological/psychiatric) disease (e.g. multiple sclerosis)
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  • Not able to give informed consent
  • Study 2: longitudinal study
  • Pre-existing cerebrovascular disease
  • Pregnancy
  • Contraindications for 3 T MRI
  • Renal function eGFR below 30 ml/min (for Dynamic Contrast Enhanced [DCE]-MRI
  • Major risk factors for acute ischemic stroke other than SVD according to the TOAST criteria,22 including, but not limited to, large-artery atherosclerosis, cardioembolism and vasculitis based on medical history and ultrasound of the carotids collected at baseline or any chronic disease that could lead to brain lesions mimicking SVD
  • Major (neurological/psychiatric) disease (e.g. multiple sclerosis)
  • Not able to give informed consent

Trial locations and contacts

1 site in 1 country.

Esther Janssen contact

+31651758279

esther.janssen@radboudumc.nl

Netherlands1 site, 1 recruiting

  • RadboudUMC

    Nijmegen, 6525GA Nijmegen

    Esther Janssen, +31651758279, esther.janssen@radboudumc.nl

    Esther Janssen

    Recruiting

Other trials in Netherlands

About this study

Official title: Midlife Hypertension and Structural and Functional Brain MRI: Catching the First Signs of Cerebral Small Vessel Disease

Cerebral small vessel disease (SVD) describes a set of pathologies affecting the smallest blood vessels in the brain. SVD contributes to up to a fifth of ischemic and hemorrhagic strokes en is the main vascular cause of dementia. On MRI, SVD is marked by different types of lesions, including white matter abnormalities, and small infarcts and hemorrhages. Recent studies indicate that SVD develops slowly over the years, starting presumably decades before the typical MRI lesions become apparent. High blood pressure plays an important role in the development of SVD MRI lesions. However, it remains unclear exactly how hypertension leads to vascular pathology. To gain more insight into how hypertension leads to SVD it is important to study mechanisms in individuals (largely) free of SVD, that is before midlife.

Therefore, the investigators aim to examine abnormalities in brain (micro) structure and vascular function in young patients with hypertension. Furthermore, the investigators aim to determine the effects of blood pressure increase and subsequent blood pressure reduction during a period of withdrawal and restart of blood pressure lowering drugs on brain (micro)structure and vascular function.

Being tested
Antihypertensive medication withdrawal
Medical subject headings
Hypertension, Cerebral Small Vessel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Antihypertensive medication withdrawalDrug

    To determine if high blood pressure is caused by an overproduction of aldosterone in the adrenal gland (i.e. primary hyperaldosteronism), the plasma aldosterone/renin ratio (ARR) can be determined. Because many common hypertensive drugs are known to interfere with this ratio, patients often have to discontinue drugs prior to screening or switch to drugs that are known not to affect ARR (i.e. doxazosin, verapamil, diltiazem, hydralazine). Drugs have to be stopped for at least four weeks (for mineralocorticoid receptor antagonists) or two weeks (for diuretics, Angiotensin Converting Enzyme (ACE) inhibitors, Angiotensin Receptor Blockers (ARBs)). This often leads to a temporary increase in blood pressure. After diagnostics are completed, medication is adjusted accordingly and blood pressure levels drop again.

Study groups in NCT06175663
Study groupRoleWhat they receive
Cross-sectional studyTo examine if there are cerebral abnormalities present following hypertension before MRI markers of SVD have manifested, we will do high-resolution 3T MRI in 100 young (18-40 years) hypertensive adults.
Longitudinal studyIn a cohort study, we will examine the effects of an increase and decrease in blood pressure on the brain. For this analysis, we will include hypertensive patients that are referred to the Radboudumc Department of Internal Medicine for a diagnostic work up on the cause(s) of their hypertension. The diagnostic procedure entails withdrawal of antihypertensives for approximately four weeks, as per the routine diagnostic protocol to allow for diagnosis of the cause of hypertension, and subsequent restart of treatment until the target blood pressure is reached (normotension). Measurements are performed just before antihypertensive medication is withdrawn (baseline), approximately four weeks after withdrawal (T=1), once patients have reached their target blood pressure and blood pressure is stable, estimated to occur within 2-4 months (T=2) and approximately 1 year after T=2 (T=3).
Receives: Drug: Antihypertensive medication withdrawal

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Standard neuroimaging markers of SVD, assessed using STRIVE criteria

    This includes white matter hyperintensity volumes, lacunes, microbleeds, DWI+ positive lesions.

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  2. DCE-MRI outcomes

    Leakage rate (Ki)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  3. DCE-MRI outcomes

    Volume fraction (Vl)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  4. DTI outcomes

    Fractional Anisotropy (FA)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  5. DTI outcomes

    Mean Diffusivity (MD)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  6. DTI outcomes

    Peak Skeleton ofMean diffusivity (PSMD)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  7. Intravoxel Incoherent Motion outcomes

    Parenchimal Diffusivity (D)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  8. Intravoxel Incoherent Motion outcomes

    Perfusion fraction (F)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  9. Intravoxel Incoherent Motion outcomes

    Microvascular perfusion (fD*)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  10. Resting state fMRI

    Functional connectivity

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

Secondary outcomes (3)

  1. Cognition

    Cognitive functioning is assessed using a 60-min cognitive assessment covering six domains: processing speed, attention, executive functioning, verbal memory, working memory and psychomotor functioning.

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  2. Motor functioning

    Motor functioning is assessed using a 6-m walking test (in seconds) and the Timed Up \& Go test (in seconds)

    Measured: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.

  3. Blood markers

    This includes circulating markers of inflammation, including cytokines and chemokines, in mmol/l measured in blood.

    Measured: Four weeks after antihypertensive drug withdrawal and after 1-4 months when blood pressure is stable.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2023
  2. Study start6 Jul 2021
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion31 Dec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
130 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06175663
Sponsor's protocol ID
NL75003.091.20
Status last verified
Dec 2023
First submitted
6 Dec 2023
Last updated
19 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Janssen E, de Jong JJA, Verburgt E, Ter Telgte A, van den Berg DTNA, Marques JP, Maas MC, Meijer FJA, Tuladhar AM, Riksen NP, Deinum J, Backes WH, de Leeuw FE. Higher Blood-Brain Barrier Permeability in Middle-Aged Adults With Hypertension. Hypertension. 2025 Dec;82(12):2172-2182. doi: 10.1161/HYPERTENSIONAHA.125.25290. Epub 2025 Oct 15.

    PubMed 41091964

Questions about this trial

What is this clinical trial studying?

An observational study of Hypertension and Small Vessel Cerebrovascular Disease, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Esther Janssen (+31651758279, esther.janssen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Standard neuroimaging markers of SVD, assessed using STRIVE criteria (time frame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06175663, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.

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Hyperintense: Midlife Hypertension and the Brain | AzTrials