--- title: Map Parkinson brain immune activity nct_id: NCT05205291 status: RECRUITING sponsor: University of Exeter study_type: OBSERVATIONAL canonical_url: "https://parkinsonspathways.com/trial/NCT05205291" clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT05205291" last_fetched: "2026-05-10T14:06:27.816Z" source: "Parkinson's Pathways (curated)" --- # Map Parkinson brain immune activity **Goal (in five words):** Map Parkinson brain immune activity **Official Title:** Molecular Imaging of LPS-induced Microglial Activation in Parkinson's Disease (PD). A TSPO PET-MR Imaging Study **Trial ID:** [NCT05205291](https://clinicaltrials.gov/study/NCT05205291) ## Key Facts - **Status:** RECRUITING - **Study Type:** OBSERVATIONAL - **Sponsor:** University of Exeter - **Target Enrollment:** 30 participants - **Start Date:** 2022-02-28 - **Completion Date:** 2026-08-31 - **Conditions:** Neurodegenerative Diseases, Parkinson Disease, REM Sleep Behavior Disorder (iRBD) - **Interventions:** Lipopolysaccharide, PET/MR with [11C]PBR28 - **Intervention Types:** DRUG, RADIATION ## Summary For Families Goal: to see where and how much brain immune cells called microglia become active in Parkinson's disease and in people with REM sleep behavior disorder, by provoking a short, controlled immune response and imaging the brain. Approach: participants receive a small, controlled dose of lipopolysaccharide to trigger innate immune activation, then have PET/MR scans with the tracer [11C]PBR28 which binds the TSPO protein on activated microglia so higher PET signal indicates more neuroinflammation; the protocol includes people who are drug-naïve or who are on stable dopaminergic therapy. Eligibility: looking for adults mainly 50 to 85 years old (iRBD arm may include 40+), including people with Parkinson's, people with iRBD, or healthy controls, who are cognitively intact, free of active inflammatory or major medical conditions, able to undergo MRI and arterial sampling, and who are not low-affinity binders for the PET tracer. ## Eligibility - **Minimum age:** 50 Years - **Maximum age:** 85 Years - **Sex:** ALL ### Full Criteria ``` Inclusion Criteria (all): * 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 * 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. Inclusion Criteria (Parkinson's disease patients): * 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: Inclusion criteria: * 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. Exclusion Criteria (all): * 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. * 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 Exclusion Criteria (Parkinson's disease patients): * 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 Exclusion criteria (for participants with iRBD): * 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 ``` ## Locations (1) - University of Exeter, Exeter, United Kingdom _(50.7236, -3.5275)_ - Holly Wrighht — (CONTACT) — h.wright3@exeter.ac.uk - Edoardo de Natale, MD MSc Ph.D — (SUB_INVESTIGATOR) ## Central 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 --- *Canonical: https://parkinsonspathways.com/trial/NCT05205291* *HTML version: https://parkinsonspathways.com/trial/NCT05205291* *Source data: https://clinicaltrials.gov/study/NCT05205291*