Hyperintense: Midlife Hypertension and the Brain

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06175663
• Other study ID #: NL75003.091.20
• Status: Recruiting
• Start date: July 6, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: December 2023
• Source: Radboud University Medical Center
• Contact: Esther Janssen
• Phone: +31651758279
• Email: esther.janssen[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Small Vessel Diseases
• Cerebrovascular Disorders
• Hypertension
• Small Vessel Cerebrovascular Disease

Intervention

Drug:
• Antihypertensive medication withdrawal
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.

Locations

Country	Name	City	State
Netherlands	RadboudUMC	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Standard neuroimaging markers of SVD, assessed using STRIVE criteria	This includes white matter hyperintensity volumes, lacunes, microbleeds, DWI+ positive lesions.	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	DCE-MRI outcomes	Leakage rate (Ki)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	DCE-MRI outcomes	Volume fraction (Vl)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	DTI outcomes	Fractional Anisotropy (FA)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	DTI outcomes	Mean Diffusivity (MD)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	DTI outcomes	Peak Skeleton ofMean diffusivity (PSMD)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	Intravoxel Incoherent Motion outcomes	Parenchimal Diffusivity (D)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	Intravoxel Incoherent Motion outcomes	Perfusion fraction (F)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	Intravoxel Incoherent Motion outcomes	Microvascular perfusion (fD*)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Primary	Resting state fMRI	Functional connectivity	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Secondary	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.	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Secondary	Motor functioning	Motor functioning is assessed using a 6-m walking test (in seconds) and the Timed Up & Go test (in seconds)	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.
Secondary	Blood markers	This includes circulating markers of inflammation, including cytokines and chemokines, in mmol/l measured in blood.	Four weeks after antihypertensive drug withdrawal and after 1-4 months when blood pressure is stable.