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

Deciphering the Mechanisms of Central Blood Pressure Regulation in Patients With Parkinson Disease Associated With Orthostatic Hypotension: A 2-phase Observational Study With Healthy Participants and Patients With Parkinson's Disease

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

Study Overview

• Status: Not yet recruiting
• Conditions: Parkinson Disease; Orthostatic Hypotension
• Intervention / Treatment: Diagnostic test: Lower body negative pressure

Detailed Description

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 (Estimated): 130

Contacts and Locations

• Study Contact: Name: Grégoire Wuerzner, Prof; Phone Number: +41 79 556 1973; Email: Gregoire.Wuerzner@chuv.ch

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Phase 1: population of healthy participants Phase 2: population of PD patients with or without OH

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy volunteers; Healthy volunteers with normal office blood pressure (<140/90 mmHg). Lower body negative pressure during brain BOLD fMRI in 3T and 7T MRI scanner.	Diagnostic test: Lower body negative pressure; 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
Parkinson patients without orthostatic hypotension; Patients with clinically established Parkinson disease, treated by dopamine replacement therapy, and without orthostatic hypotension as shown by a Schellong test. Lower body negative pressure during brain BOLD fMRI, renal contrast-enhanced ultrasound	Diagnostic test: Lower body negative pressure; 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
Parkinson patients with orthostatic hypotension; Patients with clinically established Parkinson disease, treated by dopamine replacement therapy, and having orthostatic hypotension as shown by a Schellong test. Lower body negative pressure during brain BOLD fMRI, renal contrast-enhanced ultrasound	Diagnostic test: Lower body negative pressure; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1.5 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional connectivity	Activation patterns in spatially separated brain regions tending to have synchronous activity in resting state and activation pattern change during LBNP	1.5 hour
Structural connectivity	Map of anatomical (neural) connections within the brain in PD patients with and without OH	30 minutes
Contrast-enhanced renal ultrasound	Changes in renal perfusion in response to LBNP	1.5 hour
pre-cerebral blood flow	changes in pre-cerebral blood flow in response to LBNP	30 minutes

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: University Hospital, Geneva; Ecole Polytechnique Fédérale de Lausanne
• Investigators: Principal Investigator: Grégoire Wuerzner, CHUV

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: August 18, 2025
• First Submitted That Met QC Criteria: August 18, 2025
• First Posted (Actual): August 24, 2025

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: orthostatic hypotension; parkinson disease; lower body negative pressure
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Hypotension; Parkinson Disease; Hypotension, Orthostatic
• Other Study ID Numbers: 2024-01828

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: one year after publication of the data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; 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