Brain BOLD fMRI in Hypertensive and Normotensive Participants (BRAIrdN)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension,Essential
• Intervention / Treatment: Diagnostic test: Cold Pressor test; Diagnostic test: PinPrick test

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 84

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • CHUV, nephrology service

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy normotensive participants: university employees mainly Hypertensive patients: from the outpatient clinic of the Nephrology Service Resistant hypertensive patients (renal denervated and non-denervated): from the outpatient clinic of the Nephrology Service

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1: control; 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; Both feet in icy waterbath alternated with body temperature water; Diagnostic test: PinPrick test; Pricking both feet with a needle using gravity (without penetrating) alternated with cotton swap
2: untreated hypertensive; 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; Both feet in icy waterbath alternated with body temperature water
3. resistant hypertensive; 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; Both feet in icy waterbath alternated with body temperature water
4. renal denervation; 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; Both feet in icy waterbath alternated with body temperature water

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: Ecole Polytechnique Fédérale de Lausanne

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2018
• Primary Completion (Actual): August 12, 2022
• Study Completion (Actual): August 12, 2022

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Hypertension; Kidney function; Renal denervation; Brainstem; Sympathetic nervous system; Contrast enhanced ultrasound; Blood oxygen level dependent
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: 2018-00105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data of participants that have signed the consent allowing their anonymized data to be shared, will be made available via the repository Zenodo
• IPD Sharing Time Frame: Once data are published
• IPD Sharing Access Criteria: available at zenodo :https://zenodo.org/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No