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

NCT05205291 | Recruiting

• 1 other identifier: 289952
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Neurodegenerative Diseases; Parkinson Disease; REM Sleep Behavior Disorder (iRBD)

Keywords

Positron Emission Tomography; Inflammation; Neuroimaging; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Change in inflammation in the brain following administration of LPS

  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

  36 months

Secondary Outcomes (3)

• Correlation of LPS-induced increase of inflammation and cerebral perfusion

  36 months

• Correlation of LPS-induced increase of inflammation and resting state functional MRI (rs fMRI)

  36 months

• Safety of LPS administration in Parkinson's disease patients

  36 months

Study Arms (3)

Parkinson's disease patients

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)

Drug: Lipopolysaccharide; Radiation: PET/MR with [11C]PBR28

Healthy controls

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)

Drug: Lipopolysaccharide; Radiation: PET/MR with [11C]PBR28

Patients with isolated REM sleep behavior disorder

Patients with a recent diagnosis of REM sleep behavior disorder

Interventions

Lipopolysaccharide DRUG

All participants will receive one dose of Lipopolysaccharide (1ng/Kg) after the first PET/MR scan with \[11C\]PBR28 and four hours before the second PET/MR scan with \[11C\]PBR28.

Also known as: there is no other intervention

Healthy controls; Parkinson's disease patients

PET/MR with [11C]PBR28 RADIATION

A PET/MR scan using the tracer \[11C\]PBR28 will be performed to all participants before and four hours after the administration of LPS

Also known as: there is no other intervention

Healthy controls; Parkinson's disease patients

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with Parkinson's disease: 18 in total, divided in early drug-naive Parkinson's disease (6); Parkinson's disease in pharmacological therapy(6); Advanced Parkinson's disease (6). Patients with REM sleep behavior disorder: 6 in total; Healthy volunteers (6).

You may qualify if:

• years of age, male or female
• Able to give informed consent
• Adequate visual and auditory acuity to complete the neuropsychological testing
• No presence or history of significant neurological or psychiatric disorders
• BDI ≥ 20, moderate depression
• No presence or history of inflammatory or autoimmune disorders
• Negative family history for neurodegenerative diseases
• Cognitively healthy (i.e., education-adjusted MoCA total score ≥ 26 points at screening)
• Female subjects must either be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or post-menopausal for at least 1 year (no menses for 12 months without an alternative medical cause) or if they are of childbearing potential, they must commit to use of a highly effective contraceptive measure for the duration of the study and a minimum of six months following the PET scan (including combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence).
• Male subjects and their partners of childbearing potential must commit to the use of a highly effective method of contraception during the study and for a minimum of three months following each PET scan (including, for female partners of childbearing potential, combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, male subjects with vasectomy or sexual abstinence).
• Male subjects must commit to not donate sperm during the study and for a minimum of three months after the last PET scan.
• Individuals must commit to refrain from drinking alcohol for 48 hours before each visit, refrain from drinking any caffeinated substance for 12 hours before the PET-MR visits, and to refrain from smoking or using any nicotine-containing products on the day of the PET-MR scans.
• Individuals must commit to not donating blood up to three months after the last PET scan.
• Individuals must commit to come to the screening and Day 1 visits in a fasting state (i.e., minimum of 8 hours since last meal/food intake).
• Individuals must commit to not to take any over-the-counter non-steroidal anti-inflammatory drugs or drink alcohol for 48h before screening visit.

You may not qualify if:

• Unwilling and/or unable to cooperate with study procedures
• Current or a recent (\<12 months) history of drug or alcohol abuse/dependence
• BDI ≥ 20, moderate depression
• Presence of clinically significant (as deemed by the study physician) alterations on safety laboratory blood and urine testing
• Presence of comorbidities or concomitant medications incompatible with the assessment or imaging procedures as deemed by the study physician
• Recent (less than 30 days) use of antipsychotics and corticosteroids
• Recent (less than 2 days) use of NSAIDs.
• Use of any long-acting benzodiazepines (e.g., diazepam) or use of slow or medium acting benzodiazepines with doses ≥ 30 mg within 30 days prior to the first imaging scan.
• Presence of rs6971 genotype of low-affinity binders that hinders the measure of microglial activation with \[11C\]PBR28 PET
• Presence of neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions, signs of inflammation of the CNS
• Presence of serology compatible with HIV, syphilis, SARS-CoV2, or viral hepatitis
• History of autonomic dysfunction, previous vasovagal syncope or a positive tilt-test, and with bradycardia or use of medications causing bradycardia (e.g. beta-blockers)
• Pregnancy or breastfeeding
• Contraindication to MRI, such as presence of metal devises or implants, metal deposited in the body, or metal grains in the eyes
• History of cancer within the last 5 years, except for appropriately treated, non-melanoma skin carcinoma, non-metastatic prostate cancer, treated carcinoma in situ of the cervix or Stage I uterine cancer.

Sponsors & Collaborators

• University of Exeter: lead

Study Sites (1)

University of Exeter

Exeter, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

The investigators will collect and retain venous blood samples for the analysis of inflammatory molecules (interleukines, chemokines, etc) to correlate with the imaging and clinical findings in patients with Parkinson's disease and healthy volunteers.

MeSH Terms

Conditions

Neurodegenerative Diseases; Parkinson Disease; REM Sleep Behavior Disorder; Inflammation

Interventions

Lipopolysaccharides; (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Officials

• Marios Politis, MD MSc PhD

  University of Exeter

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edoardo R. de Natale, MD MSc Ph.D

CONTACT

07503741242; e.de-natale@exeter.ac.uk

Heather Wilson, MSc Ph.D

CONTACT

07889950086; h.wilson4@exeter.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: January 25, 2022
• Study Start: February 28, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)