Hyperintense: Midlife Hypertension and the Brain

Recruiting

• Conditions: Small Vessel Cerebrovascular Disease; Hypertension
• Interventions: Drug: Antihypertensive medication withdrawal

• Registration Number: NCT06175663
• Lead Sponsor: Radboud University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-06
• Status Verified: 2023-12
• Study First Submitted: 2023-12-06
• Study First Submitted QC: 2023-12-14
• Last Update Submitted: 2023-12-14
• Study First Posted: 2023-12-19
• Last Update Posted: 2023-12-19
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Longitudinal study	Antihypertensive medication withdrawal	In 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).

Primary Outcome Measures

Name	Time	Method
Standard neuroimaging markers of SVD, assessed using STRIVE criteria	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	This includes white matter hyperintensity volumes, lacunes, microbleeds, DWI+ positive lesions.
DCE-MRI outcomes	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	Volume fraction (Vl)
Intravoxel Incoherent Motion outcomes	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	Microvascular perfusion (fD\*)
Resting state fMRI	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	Functional connectivity
DTI outcomes	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	Peak Skeleton ofMean diffusivity (PSMD)

Secondary Outcome Measures

Name	Time	Method
Motor functioning	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	Motor functioning is assessed using a 6-m walking test (in seconds) and the Timed Up \& Go test (in seconds)
Blood markers	Four weeks after antihypertensive drug withdrawal and after 1-4 months when blood pressure is stable.	This includes circulating markers of inflammation, including cytokines and chemokines, in mmol/l measured in blood.
Cognition	Baseline, four weeks after antihypertensive drug withdrawal, after 1-4 months when blood pressure is stable, 1 year later.	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.

Trial Locations

Locations (1)

RadboudUMC; 🇳🇱 Nijmegen, Netherlands