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

NCT ID: NCT07139756

Last Updated: 2025-08-24

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 130 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2028-03-31

Brief Summary

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

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

Conditions

Parkinson Disease; Orthostatic Hypotension

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Lower body negative pressure

Intervention Type: DIAGNOSTIC_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

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

Lower body negative pressure

Intervention Type: DIAGNOSTIC_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

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

Lower body negative pressure

Intervention Type: DIAGNOSTIC_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

Interventions

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• 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

• 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:

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ecole Polytechnique Fédérale de Lausanne

OTHER

Sponsor Role: collaborator

University Hospital, Geneva

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire Vaudois

OTHER

Sponsor Role: lead

Responsible Party

Gregoire Wuerzner; MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Grégoire Wuerzner

Role: PRINCIPAL_INVESTIGATOR

CHUV

Locations

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, Switzerland

Countries

Switzerland

Central Contacts

Grégoire Wuerzner, Prof

Role: CONTACT

Gregoire.Wuerzner@chuv.ch

+41 79 556 1973

Other Identifiers

2024-01828

Identifier Type: -

Identifier Source: org_study_id