A Phase 2/3 interventional study of [18F]-MFBG PET CT and [18F]-FE-PE2I PET CT or PET MRI in Parkinson Disease, Dementia with Lewy Bodies and MSA - Multiple System Atrophy, sponsored by prof. dr. Koen Van Laere. Recruiting at 2 sites in Belgium. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-02-06.
Sponsored by prof. dr. Koen Van Laere · Phase 2/3, Interventional, and Diagnostic
Study goal:
The goal of this prospective head to head comparison is to evaluate the effectiveness of [18F]-MFBG PET in assessing cardiac innervation, comparing it with [123I]-MIBG SPECT The study's primary focus is on distinguishing between Parkinson's disease (PD) and multiple system atrophy (MSA), as well as between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
Main questions:
Participant requirements:
For the main study, participants will be required to visit the hospital for 3 or 4 appointments. During these visits, they will undergo a screening visit, MRI brain scan, a comprehensive neurological assessment, [18F]-PE2I PET, [123I]-MIBG SPECT, and [18F]-MFBG PET scans.
Additionally, a separate dosimetry study will be conducted, involving healthy subjects who will visit the hospital for a screening visit and undergo [18F]-MFBG PET scans.
Study Rationale:
This prospective study, to be conducted in two centers (UZ Leuven and UZ Gent), aims to validate cardiac [18F]-MFBG PET in distinguishing Parkinson's disease (PD) from multiple system atrophy (MSA-P) and differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Both PD and DLB, caused by alpha-synuclein deposits (Lewy bodies), exhibit not only nigrostriatal dopaminergic deficits but also early peripheral changes in myocardial norepinephrine (NE) innervation. These defects can be visualized and quantified using NE transporter tracers. [18F]-MFBG was developed several years ago with high-yield production and has already been employed in multiple centers worldwide, mainly in the context of imaging neuroendocrine tumors. [18F]-MFBG offers logistical, technical, and pharmacological advantages, including faster scanning, high spatial resolution, and improved quantification compared to the existing method using [123I]-MIBG SPECT.
Participant Population:
The study will include 28 healthy volunteers (CON), of which 3 will participate in [18F]-MFBG PET dosimetry (part 1) and 25 in the main study for optimization/age-dependence of cardiac [18F]-MFBG parameters (part 2). In part 3, 40 PD, 15 MSA-P, 15 DLB, and 15 AD patients with biomarker-confirmed diagnoses will be included. Total: 113 subjects.
Intervention:
All subjects will undergo three examinations in the main work packages (parts 2 and 3) dynamic cardiac [18F]-MFBG PET, with dynamic [123I]-MIBG SPECT as a comparator, as well as cerebral [18F]-PE2I PET.
Endpoints:
Primary: Non-inferiority in discriminating populations using [18F]-MFBG; Secondary: effect size, relationship between myocardial uptake and cerebral dopamine active transporter (DAT) changes, autonomic dysfunction, regional myocardial variation.
Secondary:
4,573 studies on the registry are indexed under Parkinson Disease; 1,086 are open to participants now.
This study's planned enrollment of 113 is above the median of 40 across 3,353 interventional studies indexed under Parkinson Disease.
Browse Parkinson Disease studies →prof. dr. Koen Van Laere is the lead sponsor of 2 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Healthy Controls:
Parkinson's Disease:
Multiple System Atrophy - Parkinsonian Variant:
Dementia Due to Alzheimer's Disease:
Dementia with Lewy Bodies:
Exclusion Criteria:
Healthy controls:
Parkinson's Disease:
Multiple System Atrophy - Parkinsonian Variant:
Dementia Due to Alzheimer's Disease:
Dementia with Lewy Bodies:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
25 healthy subjects (5 young 20-40y and 20 between 50-85y) will be enrolled for the head-to-head comparison with \[18F\]-MFBG, \[123I\]-MIBG and \[18F\]-FE-PE2I (Part 2). In 5 healthy controls, arterial sampling will be carried out for kinetic modelling.
Diagnostic Test: [18F]-MFBG PET CT · Diagnostic Test: [18F]-FE-PE2I PET CT or PET MRI · Diagnostic Test: [123I]-MIBG SPECT CT
In total, 40 PD patients will be included. In order to determine relationships with disease progression, two subgroups will be included with disease duration up to 5 years and 5 years or more respectively. In total, 15 MSA-P patients will be enrolled. For both groups, abnormal previous \[18F\]-FE-PE2I or \[123I\]-FP-CIT SPECT scan is required. Head-to-head comparison with \[18F\]-MFBG, \[123I\]-MIBG and \[18F\]-FE-PE2I (Part 3).
Diagnostic Test: [18F]-MFBG PET CT · Diagnostic Test: [18F]-FE-PE2I PET CT or PET MRI · Diagnostic Test: [123I]-MIBG SPECT CT
In total 15 patients with probable DLB (including biomarker selection through abnormal previous \[18F\]-FE-PE2I or \[123I\]-FP-CIT SPECT scan) and 15 patients with probable AD (including biomarker proven amyloid-beta positivity either by cerebrospinal fluid biomarker analysis or by \[18F\]-NAV4694 imaging as standard of care). Head-to-head comparison with \[18F\]-MFBG, \[123I\]-MIBG and \[18F\]-FE-PE2I (Part 3).
Diagnostic Test: [18F]-MFBG PET CT · Diagnostic Test: [18F]-FE-PE2I PET CT or PET MRI · Diagnostic Test: [123I]-MIBG SPECT CT
For dosimetry of \[18F\]-MFBG only, 3 subjects (18-80 y) will be enrolled (Part 1).
Diagnostic Test: [18F]-MFBG PET dosimetry scans
\[18F\]-MFBG will be acquired at the Leuven University hospital on a GE MI4 PET/CT camera, with low dose CT and 120 MBq injected activity. Dynamic imaging between 0-60 minutes and 100-120 minutes (patients) and 0-70 minutes and 90-120 minutes (healthy volunteers). Venous sampling between 5-120 minutes will be obtained through a second catheter, 6 venous samples will be taken. In healthy up to 5 control subjects, full arterial sampling (0-120 minutes,) will also be done. If patient comfort allows, after the dynamic cardiac scan 2 hours post-injection field dynamic scan, a fast late timepoint whole body PET/CT will be taken (2 min/bed position, 11 mAs low dose CT; estimated 10-12 minutes).
\[18F\]-FE-PE2I will be performed at the University Hospital Leuven with the GE Signa simultaneous PET/MR with acquisition at 50-70 minutes postinjection or at the University Hospital in Gent using a Siemens PET/CT, GE MI4 PET/CT. Injected activity: 120 MBq
\[123I\]-MIBG SPECT/CT (low dose CT) will be performed at the local nuclear medicine department of each participating center. Injected activity: 111 MBq
\[18F\]-MFBG will be acquired at the Leuven University hospital on a Siemens Truepoint or GE MI4 PET/CT camera or equivalent newer camera, with low dose CT and 120 MBq injected activity. Three segments of consecutive whole-body scanning with increasing bed position duration will be carried out up to 3 half-lives (physical half-life T1/2 for 18F = 110 minutes): from 0-90 minutes (scan 1-8), 120-150 (scan 9) and 300-330 (scan 10) minutes post injection. In total 10 whole body biodistribution scans will be taken. Urine will be collected and its total activity measured to measure bladder excretion for correction of integrated bladder organ residence. Before each segment, a low dose whole body CT scan (11 mAs) will be acquired for attenuation correction and organ delineation.
Difference in diagnostic accuracy between [18F]-MFBG and [I123]-MIBG
Diffirence in diagnostic accuracy ((sensitivity) (prevalence) + (specificity) (1 - prevalence)) of \[18F\]-MFBG versus \[I123\]-MIBG in differentiating PD versus MSA-P and LBD versus AD. The index test is semi-quantitative analysis or visual inspection of the change in myocardial uptake of the tracer. Semi-quantitative analysis will be based on \[18F\]-MFBG myocardial volume of distribution (VT) in L/kg, early and late standardized uptake volume (SUV) in g/ml , heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage. The reference test is the previously established clinical diagnosis.
Time frame: Diagnostic accuracy will be calculated when the scans of the PD and MSA panels have been completed and again when scanning of DLB and AD panels has been completed (estimated 3 years after study start).
Effect size
For all subjects, the \[18F\]-MFBG myocardial volume of distribution (VT) in L/kg, early and late standardized uptake volume (SUV) in g/ml , heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage will be calculated. For cardiac \[123I\]-MIBG SPECT, early and late HMR and WR values will be calculated. The effect sizes will be calculated between groups for both tracers through Cohen's d or another relevant effect size measure, depending on the data distribution and scale. Direct comparison of the effect size of the difference in \[18F\]-MFBG and \[123I\]-MIBG myocardial uptake in PD versus healthy controls and MSA-P and DLB versus healthy controls and AD.
Time frame: Effect size will be calculated when all scans have been completed (estimated 3 years after study start).
Relation to brain DAT
For all subjects, the \[18F\]-MFBG myocardial volume of distribution (VT) in (L/kg), early and late standardized uptake volume (SUV), heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage will be calculated. For the same subjects, the \[18F\]-FE-PE2I binding potential in left and right caudate and putamen, with reference to the occipital neocortex, will be calculated. For each panel (HC and each patient group), the mean and standard deviation for each test and outcome parameter will be calculated and the measurements will be converted to Z scores. The resulting Z scores will be plotted on a scatter plot and the Pearson correlation coefficient or other correlation measures will be calculated to test for a relation between the two tests.
Time frame: The relation to brain DAT will be calculated when the scans of PD, DLB and HC groups have been completed (estimated 3 years).
Correlation of myocardial uptake of [18F]-MFBG to autonomic dysfunction
Autonomic dysfunction will be assessed using the SCOPA-AUT scale and by testing for neurogenic orthostatic hypotension. The SCOPA-AUT scale result will be expressed as a single numerical score by assigning a value of 0, 1, 2, 3 to the options and adding up the values for all the questions. A higher score means more symptoms linked to autonomic dysfunction. Myocardial uptake of \[18F\]-MFBG in PD and DLB will be measured and expressed in VT in L/kg or WR as a percentage. The correlation between the SCOPA-AUT scores and \[18F\]-MFBG myocardial uptake will be assessed by calculating Spearman's Rank Correlation Coefficient or another statistical measure. The relationship between measure neurogenic orthostatic hypotension (present/absent) and myocardial uptake of \[18F\]-MFBG will be assessed by Point-Biserial Correlation Coefficient or another statistical measure.
Time frame: The relation to autonomic dysfunction will be calculated when the scans of PD and DLB patients have been completed (estimated 2 years after study start)..
Utility of regional myocardial parameter variation
The myocardial \[18F\]-MFBG uptake will be projected on a polar map of the myocardium comprised of 17 segments. For each segment, scores such as regional wash-out (rWO), and regional myocardial tracer uptake (VT, HRM) will be calculated. These regional values will be compared between groups by two-way ANOVA or another statistical method and post-hoc analysis. The endpoint will be met if different regional segment scores are present between PD/MSA-P or DLB/AD or subtypes of PD.
Time frame: The regional myocardial parameter variation will be calculated when the scans of patient groups have been completed (estimated 3 years after study start).
Plan to share: No
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Started Jan 2024 (actual). Primary completion is estimated for Jul 2026, 30 months after the start.
Of 22 phase 2/3 interventional studies under Parkinson Disease, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 50. This study's planned 30 months is above that.
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prof. dr. Koen Van Laere