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

Vaud University Hospital Center

Status: Not yet enrolling

Conditions: Parkinson Disease; Orthostatic Hypotension

Treatments: Diagnostic Test: Lower body negative pressure

Study type: Observational

Funder types: Other

Identifiers

NCT07139756

2024-01828

Details and patient eligibility

About

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

Full 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

Enrollment: 130 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

130 participants in 3 patient groups

Healthy volunteers

Description:

Healthy volunteers with normal office blood pressure (\<140/90 mmHg). Lower body negative pressure during brain BOLD fMRI in 3T and 7T MRI scanner.

Treatment:

Diagnostic Test: Lower body negative pressure

Parkinson patients without orthostatic hypotension

Description:

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

Treatment:

Diagnostic Test: Lower body negative pressure

Parkinson patients with orthostatic hypotension

Description:

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

Treatment:

Diagnostic Test: Lower body negative pressure