AzTrials
AzTrials

Neurodegenerative DiseasesNCT05205291

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

An observational study of Neurodegenerative Diseases and Parkinson Disease, run by University of Exeter at 1 site in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 50 to 85 yearsHealthy volunteers can take part
What is being tested?
Lipopolysaccharide and PET/MR with [11C]PBR28
Type of treatment
Surgery or procedure
How many people
30 participants
Where
1 siteUnited Kingdom
Study dates
28 Feb 2022to 31 Aug 2026
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

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).

Who may be able to join

  • 50-85 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
Show all 46Show fewer
  • 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.
  • 50-85 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 other significant neurological or psychiatric disorders
  • Diagnosis of PD according to the Movement Disorder Society Clinical Diagnostic Criteria (Postuma et al., Mov Disord 2015)
  • Drug-naïve participants with PD must have a diagnosis of PD but must be therapy-free at the time of enrolment
  • For participants with PD-MCI: diagnosis of MCI according the diagnostic criteria for MCI-PD (Level I; Litvan et al., Mov Disord 2012) and/or MoCA < 23
  • For participants with PD taking dopaminergic therapy: must be in stable therapy (i.e. not have changed therapy in the last 60 days)
  • 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.
  • For participants with iRBD:
  • 40-85 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-II ≥ 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.

Who cannot join

  • 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
Show all 62Show fewer
  • 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.
  • Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable
  • Contraindication to arterial cannulation, such as history of bleedings, haemorrhage, etc.
  • Negative Allen's test (i.e. absence of collateral flow on hands on the test)
  • Recent (less than 30 days) infection or vaccination (e.g. flu, SARS-CoV2 etc.)
  • Concurrent participation to any clinical trial testing investigational drugs
  • Unwilling and/or unable to cooperate with study procedures
  • Current or recent 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 or 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 other neurological disorders and known intracranial co-morbidities such as stroke, haemorrhage, space-occupying lesions, signs of inflammation of the CNS
  • 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)
  • Presence of serology compatible with HIV, syphilis, SARS-CoV2, or viral hepatitis
  • 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.
  • Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable
  • Contraindication to arterial cannulation, such as history of bleedings, haemorrhage, etc.
  • Negative Allen's test (i.e. absence of collateral flow on hands on the test)
  • Recent (less than 30 days) infection or vaccination (e.g. flu, SARS-CoV2 etc.)
  • Concurrent participation to any clinical trial testing investigational drugs
  • Unwilling and/or unable to cooperate with study procedures
  • Current or a recent (<12 months) history of drug or alcohol abuse/dependence
  • BDI-II ≥ 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.
  • Use of any of the following drugs that might interfere with dopamine transporter SPECT imaging: Ephedrine, ketamine, isoflurane, cocaine, methylphenidate, amphetamine of any amphetamine derivatives, mazindol, modafinil, benztropine, fentanyl, derivatives, buproprion, phentermine neuroleptics, metoclopramide, alpha methyldopa, , reserpine, .
  • 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, 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.
  • Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable
  • Contraindication to arterial cannulation, such as history of bleedings, haemorrhage, etc.
  • Negative Allen's test (i.e. absence of collateral flow on hands on the test)
  • Recent (less than 30 days) infection or vaccination (e.g. flu, SARS-CoV2 etc.)
  • Evidence of presynaptic dopaminergic denervation on [123I]FP-CIT SPECT
  • Concurrent participation to any clinical trial testing investigational drugs

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

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

United Kingdom1 site, 1 recruiting
  • University of Exeter

    Exeter

    Holly Wrighht, h.wright3@exeter.ac.uk

    Edoardo de Natale, MD MSc Ph.D

    Recruiting

Other trials in United Kingdom

About this study

Official title: Molecular Imaging of LPS-induced Microglial Activation in Parkinson's Disease (PD). A TSPO PET-MR Imaging Study

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.

Read the 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.

Being tested
Lipopolysaccharide, PET/MR with [11C]PBR28
Keywords
Positron Emission Tomography, Inflammation, Neuroimaging, Biomarkers
Medical subject headings
Neurodegenerative Diseases, Parkinson Disease, REM Sleep Behavior Disorder, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LipopolysaccharideDrug

    Also called there is no other intervention

    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.

  • PET/MR with [11C]PBR28Radiation

    Also called there is no other intervention

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

Study groups in NCT05205291
Study groupRoleWhat they receive
Parkinson's disease patients18 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)
Receives: Drug: Lipopolysaccharide; Radiation: PET/MR with [11C]PBR28
Healthy controls6 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)
Receives: Drug: Lipopolysaccharide; Radiation: PET/MR with [11C]PBR28
Patients with isolated REM sleep behavior disorderPatients with a recent diagnosis of REM sleep behavior disorder

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 36 months

Secondary outcomes (3)
  1. Correlation of LPS-induced increase of inflammation and cerebral perfusion

    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

    Measured: 36 months

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

    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

    Measured: 36 months

  3. Safety of LPS administration in Parkinson's disease patients

    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.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2022
  2. Study start28 Feb 2022
  3. Primary completion31 Aug 2026 (estimated)
  4. Study completion31 Aug 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Cross-sectional
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05205291
Sponsor's protocol ID
289952
Status last verified
Oct 2025
First submitted
9 Nov 2021
Last updated
7 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

An observational study of Neurodegenerative Diseases and Parkinson Disease, run by University of Exeter at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 62 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Edoardo R. de Natale, MD MSc Ph.D (07503741242, e.de-natale@exeter.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in inflammation in the brain following administration of LPS (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2025.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in