Clinical trial NCT06175663: Hyperintense: Midlife Hypertension and the Brain
Official title: Midlife Hypertension and Structural and Functional Brain MRI: Catching the First Signs of Cerebral Small Vessel Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertension
Small Vessel Cerebrovascular Disease
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2023-12-19
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.


Eligibility criteria: Study 1: cross-sectional study

Inclusion Criteria:

* Age 18-40 years
* Blood pressure above 140/90 mmHg, measured within three months prior to study participation

Exclusion Criteria:

* 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)
* Not able to give informed consent

Study 2: longitudinal study

Inclusion criteria:

* Age 18-55 years
* Undergoing diagnostic routine of temporary antihypertensive withdrawal for biochemical analysis as part of clinical work-up

Exclusion criteria:

* 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

Primary outcomes:
measure: Standard neuroimaging markers of SVD, assessed using STRIVE criteria
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: DCE-MRI outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: DCE-MRI outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: DTI outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: DTI outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: DTI outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: Intravoxel Incoherent Motion outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: Intravoxel Incoherent Motion outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: Intravoxel Incoherent Motion outcomes
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: Resting state fMRI
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Secondary outcomes:
measure: Cognition
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: Motor functioning
timeFrame: Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
measure: Blood markers
timeFrame: Four weeks after antihypertensive drug withdrawal and after 1-4 months when blood pressure is stable.
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: RadboudUMC
Study officials:
affiliation: Radboud University Medical Center
name: Frank-Erik de Leeuw
role: PRINCIPAL_INVESTIGATOR
References: