Deciphering the Mechanisms of Central BP Regulation in Patients With PD Associated With Orthostatic Hypotension

N/ANot Yet RecruitingNCT07139756

Centre Hospitalier Universitaire Vaudois130 enrolled

Overview

Phase 1 objective: test the feasibility of using a 3Tesla MRI scanner instead of a 7Tesla MRI scanner to measure brainstem responses to LBNP in healthy participants. Phase 2 primary objective: compare the brainstem responses to LBNP in patients with PD associated with OH to PD patients without OH using BOLD fMRI

Phase 1 objective: test the feasibility of using a 3Tesla MRI scanner instead of a 7Tesla MRI scanner to measure brainstem responses to LBNP in healthy participants using BOLD fMRI Phase 2 primary objective: compare the brainstem responses to LBNP in patients with PD associated with OH to PD patients without OH using BOLD fMRI Phase 2 secondary objectives: * assess modulation of functional connectivity in response to LBNP (effective connectivity analysis by psycho-physiological interactions (PPI)) and determine differences between the two groups * assess functional connectivity in resting state and determine differences between the two groups * compare structural connectivity in both groups using tractography * compare renal response to LBNP in both groups using contrast-enhanced ultrasound * compare pre-cerebral flow response to LBNP in both groups

Study Type

OBSERVATIONAL

Enrollment

130

Conditions

Parkinson Disease Orthostatic Hypotension

Interventions

Lower body negative pressureDIAGNOSTIC_TEST

LBNP is a technique that redistributes blood from the upper body to the dependent regions of the legs, thus reducing central venous pressure and venous return and thereby activating the sympathetic nervous system (SNS). The subject is placed in a cylindrical airtight tank, which is sealed at the level of the iliac crests, and sub-atmospheric pressure is produced using a vacuum pump. It can be used to characterize the cardiovascular responses to orthostatic stress

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Phase 1: Inclusion Criteria: * Signed informed consent * Age ≥ 18 years and \<75 years * Normal office blood pressure (\<140/90 mmHg) * For women of childbearing potential: using or willing to use during the study a reliable contraception method compatible with MRI Exclusion Criteria: * Schellong test showing OH (drop of Systolic BP \>20 mmHg or Diastolic BP \>10 mmHg) * Pregnant or lactating women * Refusal to be informed of incidental findings * Any medication (acute or chronic prescription) except oral contraception * Clinical significant abnormal blood test as assessed by the investigator * Chronic or acute illness * Concomitant participation in a clinical trial * Blood donation in the 60 previous days * Contra-indications for MRI * Unable to follow study procedures * Having a hierarchical relationship with the investigator or being family of the investigator Phase 2: Inclusion Criteria: * Signed informed consent * Fulfilling Movement Disorder Society clinical criteria for "clinically established PD" * Age ≥18 years and \<75 years * PD treated by dopamine replacement therapy (DRT) * Willing and able to comply with the visit schedule and study procedures * Autonomous in daily life * Schellong test showing OH (drop of Systolic BP \>20 mmHg or Diastolic BP \>10 mmHg)(for study group with OH) or no OH (for studygroup without OH) * For women of childbearing potential: using or willing to use during the study a reliable contraception method compatible with MRI Exclusion Criteria: * Unable to give an informed consent * BP \> 180/110 mmHg on 24-hour ambulatory blood pressure monitoring * eGFR \< 45 ml/min/1.73 ml/min/m2 by CKD-EPI equation * having contra-indications for MRI * Pregnant or lactating women * Refusal to be informed of incidental findings * Allergy to components of contrast agent Sonovue® * Living in an institution * Dementia * Type 2 diabetes * Stroke or myocardial infarction in the past 6 months * Blood donation in the previous 6 months * Active oncology treatment * Having a hierarchical relationship with the investigator or being family of the investigator

Locations (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, Switzerland

Outcomes

Primary Outcomes

Differences and changes in BOLD fMRI signal intensity

Changes in brain BOLD fMRI signal in the dorsolateral medulla of the brainstem in response to LBNP

Time frame: 1.5 hour

Secondary Outcomes

Functional connectivity

Activation patterns in spatially separated brain regions tending to have synchronous activity in resting state and activation pattern change during LBNP

Time frame: 1.5 hour

Structural connectivity

Map of anatomical (neural) connections within the brain in PD patients with and without OH

Time frame: 30 minutes

Contrast-enhanced renal ultrasound

Changes in renal perfusion in response to LBNP

Time frame: 1.5 hour

pre-cerebral blood flow

changes in pre-cerebral blood flow in response to LBNP

Time frame: 30 minutes

Central Contacts

Grégoire Wuerzner, Prof

CONTACT

+41 79 556 1973 Gregoire.Wuerzner@chuv.ch

Data from ClinicalTrials.gov

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