Brain BOLD fMRI in Hypertensive and Normotensive Participants

Study Overview
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Brief Summary
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This study will explore the brainstem activity in response to stress in hypertensive patients and normotensive subjects. In addition, it will evaluate if the response in hypertensive patients can be modulated by blocking the afferent signalling of sympathetic nervous system from the kidney to the brain achieved by renal denervation. The investigators hypothesize that the change in BOLD signal intensity in response to stress is higher in hypertensive patients than in normotensive subjects and that in patients responsive to renal denervation the change in BOLD signal intensity in response to stress is decreased compared to non-responders or to non-denervated resistant hypertensive patients.

Detailed Description
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In hypertension, the overactivity of the sympathetic nervous system (SNS) has been found to be implicated in its initiation, maintenance and adverse consequences. The SNS is composed of an afferent and efferent arm, which brings sensory information to the brain (e.g. brainstem and hypothalamus) and transmits sympathetic outflow from the brain to the peripheral organs, respectively. Selective removal of the afferent renal component of the SNS can modulate central sympathetic outflow to the kidney, heart and vasculature in animals. The specific contribution of afferent nerve signalling in hypertension and in the potential antihypertensive effect of renal denervation has not been studied in humans.

Official Title
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Central Blood Pressure Regulation by the Brainstem and Influence by Renal Sympathetic Afference: a Functional Magnetic Resonance Imaging (MRI) Study in Hypertensive and Normotensive Participants

Conditions
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Hypertension,Essential

Intervention / Treatment
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* Diagnostic Test: Cold Pressor test
* Diagnostic Test: PinPrick test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed informed consent capable of discernment Exclusion Criteria: having contra-indications for MRI (claustrophobia, cardiac pacemaker or other metallic or mechanical implant or device, etc.) pregnant women lower limb sensitive neuropathy Blood pressure >180/110 mmHg during washout period (for hypertensive patients) Intolerance to Sonovue®(ultrasound contrast agent) Acute or chronic disease other than hypertension that influences renal function taking medication/drugs, except of calcium channel blockers for resistant hypertensive patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1: control<br>Healthy normotensive participants. Cold pressor test on feet 3 times for 40 seconds during brain BOLD fMRI (2 runs), renal ultrasound and contrast-enhanced ultrasound. PinPrick test on feet 3 times for 40 seconds during brain BOLD fMRI (2 runs), renal ultrasound and contrast-enhanced ultrasound. | Diagnostic Test: Cold Pressor test<br>* Both feet in icy waterbath alternated with body temperature water<br>Diagnostic Test: PinPrick test<br>* Pricking both feet with a needle using gravity (without penetrating) alternated with cotton swap<br>|
| 2: untreated hypertensive<br>Untreated (or off antihypertensive drugs) hypertensive patients (ABPM proven essential hypertension). Cold pressor test on feet 3 times for 40 seconds during BOLD fMRI (2 runs), renal ultrasound and contrast-enhanced ultrasound. | Diagnostic Test: Cold Pressor test<br>* Both feet in icy waterbath alternated with body temperature water<br>|
| 3. resistant hypertensive<br>Patients with proven resistant hypertension and not renal denervated or for whom a renal denervation is planned according to the criteria of the CHUV. Cold pressor test on feet 3 times for 40 seconds during BOLD fMRI (2 runs), renal ultrasound and contrast-enhanced ultrasound. | Diagnostic Test: Cold Pressor test<br>* Both feet in icy waterbath alternated with body temperature water<br>|
| 4. renal denervation<br>Patients with a renal denervation. Cold pressor test on feet 3 times for 40 seconds during BOLD fMRI (2 runs), renal ultrasound and contrast-enhanced ultrasound. | Diagnostic Test: Cold Pressor test<br>* Both feet in icy waterbath alternated with body temperature water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in brain BOLD signal intensity | Changes in the brain BOLD fMRI signal of the brainstem in response to a cold pressor test | 1.5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional connectivity (resting state and effective connectivity) | Activation patterns in spatially separated brain regions tending to have synchronous activity in resting state and activation pattern changes during a cold pressor test | 1.5 hours | 
| Structural connectivity | Map of anatomical (neural) connections within the brain in normotensive subjects and hypertensive patients | 30 minutes | 
| Correlation between brain BOLD fMRI and renal ultrasound | Correlation between changes in brain BOLD signal and renal (contrast-enhanced) ultrasound endpoints | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sympathetic nervous system, Blood oxygen level dependent, Brainstem, Contrast enhanced ultrasound, Kidney function, Hypertension, Renal denervation