Molecular Imaging of Inflammation in Parkinson's Disease Using LPS and TSPO-PET/MR

Recruiting

• Conditions: Neurodegenerative Diseases; Parkinson Disease
• Interventions: Drug: Lipopolysaccharide; Radiation: PET/MR with [11C]PBR28

• Registration Number: NCT05205291
• Lead Sponsor: University of Exeter

Brief Summary

It is not known what causes Parkinson's disease and what makes it worsen over time. Research conducted in the past few years has highlighted the possible role of inflammation on this process but its actual mechanisms are still obscure.

In this study, the investigators aim to gain understanding on how inflammation is increased in Parkinson's disease and what are its mechanisms, by performing two Positron Emission Tomography (PET) scans using the tracer \[11C\]PBR28, that takes pictures of the brain highlighting the areas of inflammation, before and after the administration of a compound called Lipopolysaccharide or LPS, that is known to cause a mild degree of inflammation. The investigators will couple this study with two venous blood draws to measure the levels of circulating molecules of inflammation.

Detailed Description

This is a cross-sectional study.

The study will be divided in two visits, of which, the visit 1 will take place in Exeter, and visit 2 will take place in London.

During visit 1, the participants will attend the NIHR Clinical Research Facility of Royal Devon \& Exeter NHS Foundation Trust. The study doctor will explain all study procedures in a lay language and will answer all the participants' queries. After that, if they agree to participate, they will sign the informed consent. After this procedure, the study doctor will ask a few questions and assess whether the participant is suitable to be enrolled in the study. Then, the study doctor will undertake a clinical examination, and make some tests (questionnaires) to assess the presence of symptoms related to movement, thinking, memory, and behaviour. Finally, the study doctor will collect some blood and urine, for safety laboratory exams. Women of childbearing potential will also have a pregnancy test, for safety in view of the PET scans. After these procedures, the participants will be accompanied to the Mireille Gillings Neuroimaging Centre, that lies just opposite the Clinical Research Facility, and where they will perform the MRI scan. The MRI scan will collect pictures of the brain and will serve to gather information about the structure of the brain of the patients, and to exclude the concomitant presence of any lesion (incidental findings). The whole duration of the visit will be of around 3 hours, also counting the time for taking the consent and for the MRI scan.

During visit 2, the participants will attend the NIHR Imperial Clinical Research Facility and Invicro, in West London, over two consecutive days.

In the first day, the participants will attend the NIHR Imperial Clinical Research facility for a clinical visit to assess any change in medication or any side effect. Patients with Parkinson's disease will answer a few questionnaires on presence of symptoms related to PD. If more than 60 days have passed from the screening visit, participants will repeat the urine collection for safety analysis.

The participants (and one companion, if needed) will then be accompanied to the accommodation for the night, that is located just next to the MIHR Imperial Clinical Research Facility.

In the second day, the participants will attend Invicro for the PET visit. Invicro is a specialized centre for research on neuroimaging and is located opposite the accommodation facility. They will undergo a venous cannulation (for the injection of the tracer for the PET scans and for the injection of LPS) and an arterial cannulation (to collect some blood during the PET scans, that will serve to help with the analysis of the scans). the first PET scan will take place in the morning. After the PET scan, the participant will undergo the administration of LPS at the dose of 1 ng/Kg. Since LPS can cause side effects linked to neuroinflammation, the patient will have the blood pressure, heart rate, respiratory rate, and cardiac rhythm monitored for six hours, that is the mean duration of the effect of LPS. After four hours from the injection of LPS, the participants will undergo a second PET scan. The whole duration of the visit will be of around 8 hours. At the end of this visit, a sample of blood will be collected to repeat the safety laboratory tests. After this visit, the participants will be asked to attend the NIHR Imperial Clinical Research Facility for an overnight stay to monitor for any side effect, under medical supervision by a qualified doctor on call. After the overnight stay, if there won't be any side effect, the participant can be discharged and will have finished the study.

Study Timeline

• Study First Submitted: 2021-11-09
• Study First Submitted QC: 2022-01-24
• Study First Posted: 2022-01-25
• Study Start: 2022-02-28
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-10
• Primary Completion: 2025-08-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy controls	Lipopolysaccharide	6 healthy controls who will undergo clinical assessment, and PET/MR imaging of TSPO using the tracer \[11C\]PBR28 before and four hours after administration of LPS (1 ng/Kg)
Parkinson's disease patients	Lipopolysaccharide	18 patients with Parkinson's disease who will undergo clinical assessment, and PET/MR imaging of TSPO using the tracer \[11C\]PBR28 before and four hours after administration of LPS (1 ng/Kg)
Parkinson's disease patients	PET/MR with [11C]PBR28	18 patients with Parkinson's disease who will undergo clinical assessment, and PET/MR imaging of TSPO using the tracer \[11C\]PBR28 before and four hours after administration of LPS (1 ng/Kg)
Healthy controls	PET/MR with [11C]PBR28	6 healthy controls who will undergo clinical assessment, and PET/MR imaging of TSPO using the tracer \[11C\]PBR28 before and four hours after administration of LPS (1 ng/Kg)

Primary Outcome Measures

Name	Time	Method
Change in inflammation in the brain following administration of LPS	36 months	To evaluate whether the activation of microglia following administration of LPS, as measured with PET/MR and the tracer \[11C\]PBR28, is changed in patients with Parkinson's disease compared with healthy volunteers

Secondary Outcome Measures

Name	Time	Method
Correlation of LPS-induced increase of inflammation and cerebral perfusion	36 months	To evaluate whether the administration of LPS increases the cerebral perfusion, as measured with Arterial Spin Labelling (ASL) in patients with Parkinson's disease compared with healthy volunteers
Correlation of LPS-induced increase of inflammation and resting state functional MRI (rs fMRI)	36 months	To evaluate whether the administration of LPS changes resting state functional Magnetic Resonance Imaging (rs-fMRI) parameters, which measure the strength of functional connectivity in the brain, in patients with Parkinson's disease compared with healthy volunteers
Safety of LPS administration in Parkinson's disease patients	36 months	To evaluate whether the administration of LPS is safe to use as a paradigm of in vivo study of inflammation in patient with Parkinson's disease, as measured by the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and by overnight monitoring of the participants.

Trial Locations

Locations (1)

University of Exeter; 🇬🇧 Exeter, United Kingdom