Ultra-High Resolution PET of the Human Brain and Spinal Cord in Healthy Aging, Dementia, Movement Disorders, ALS and Psychotic Disorders

Plain English Summary

Ultra-High Resolution PET in Aging, Neurodegeneration and Psychotic Disorders is a Not Applicable clinical trial sponsored by Universitaire Ziekenhuizen KU Leuven studying Alzheimer Dementia (AD), ALS - Amyotrophic Lateral Sclerosis, Parkinson s Disease, REM Sleep Behavior Disorder (iRBD), PSP - Progressive Supranuclear Palsy, MSA - Multiple System Atrophy, Dementia With Lewy Bodies (DLB), ALS With Frontotemporal Dementia (ALS/FTD), Adult Onset Psychotic Disorder, Very Late Onset Psychotic Disorder. This study uses a new, highly detailed brain imaging technique (PET scans) to understand changes in the brain and spinal cord. It is for healthy individuals and patients with conditions like Alzheimer's, Parkinson's, ALS, or psychotic disorders. Participation involves brain scans (PET and MRI) and cognitive/clinical assessments. Alternatives include standard diagnostic tests and existing treatments, but this study offers a deeper look at brain changes. The trial aims to enroll 300 participants.

Official Summary

The goal of this study is to use ultra-high-resolution (UHR) PET imaging to better understand how the brain and spinal cord change in healthy aging and in neurological and psychiatric disorders such as Alzheimer's disease (AD), Parkinson's disease and related movement disorders, amyotrophic lateral sclerosis (ALS), and psychotic disorders. Researchers will use the NeuroExplorer PET/CT system, a new scanner that can show very small structures in the brain and spinal cord in much more detail than regular PET. The main questions this study aims to answer are: * How do small but important brain regions (like the locus coeruleus, substantia nigra, and thalamic nuclei) change in healthy aging? * What early brain changes occur in neurodegenerative and psychotic disorders, and can they help improve early diagnosis? Participants will: * Undergo PET and MRI brain scans using different tracers that measure brain metabolism (18F-FDG), synaptic density (¹⁸F-SynVesT-1), dopamine transporters (¹⁸F-PE2I), and tau protein buildup (¹⁸F-MK6240). * Complete cognitive and clinical assessments related to memory, mood, and motor or psychiatric symptoms, depending on their group. This study will include healthy volunteers and patients with mild cognitive impairment due to Alzheimer´s disease, ALS, Parkinson's disease and related disorders, or psychotic disorders. The results will help create detailed brain imaging maps for healthy aging and identify early biomarkers for different diseases to support better diagnosis and treatment in the future.

Who Can Participate

Here is what you need to know about eligibility for this trial. Individuals aged 18-90 who are generally healthy or have a confirmed diagnosis in specific neurological or psychiatric categories. Exclusion criteria include other major neurological or psychiatric conditions, substance abuse, certain medications, or conditions preventing MRI scans (like claustrophobia). Specific criteria apply to each group, such as biomarker-proven Alzheimer's, meeting ALS diagnostic criteria, or specific movement disorder diagnoses. Participants must be able to undergo the scans and assessments, and provide informed consent. This trial is studying Alzheimer Dementia (AD), ALS - Amyotrophic Lateral Sclerosis, Parkinson s Disease, REM Sleep Behavior Disorder (iRBD), PSP - Progressive Supranuclear Palsy, MSA - Multiple System Atrophy, Dementia With Lewy Bodies (DLB), ALS With Frontotemporal Dementia (ALS/FTD), Adult Onset Psychotic Disorder, Very Late Onset Psychotic Disorder, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how much of specific substances are taken up in small brain areas, which helps researchers understand brain metabolism, dopamine activity, and protein buildup, indicating The specific primary outcome measures are: Volume distribution (mL/cm³) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240 (Through study completion, an average of 4 year); Standardized uptake value ratios (SUVR) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240 (Through study completion, an average of 4 year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial is important for developing earlier and more accurate diagnoses of neurodegenerative and psychotic disorders by mapping subtle brain changes with unprecedented detail. This research targets Alzheimer Dementia (AD), ALS - Amyotrophic Lateral Sclerosis, Parkinson s Disease, REM Sleep Behavior Disorder (iRBD), PSP - Progressive Supranuclear Palsy, MSA - Multiple System Atrophy, Dementia With Lewy Bodies (DLB), ALS With Frontotemporal Dementia (ALS/FTD), Adult Onset Psychotic Disorder, Very Late Onset Psychotic Disorder, where improved treatment options are needed.

Investor Insight

This study leverages cutting-edge PET technology to map brain changes in a large patient population, potentially leading to new diagnostic tools and treatments for major neurological and psychiatric c

Is This Trial Right for Me?

Ask your doctor if this advanced imaging could provide insights into your condition or if you qualify for the study. Be prepared for multiple appointments involving brain scans (PET and MRI) and cognitive or physical tests. The scans involve lying still in a scanner for a period, and different substances (tracers) will be used to highlight specific brain functions or changes. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 300 participants

Interventions

• OTHER: UHR PET/CT scan of the brain with ¹⁸F-FDG — Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism
• OTHER: UHR PET/CT scan of the brain with ¹⁸F-PE2I — Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-PE2I radiotracer to assess dopaminergic activity
• OTHER: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1 — Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-SynVesT-1 radiotracer to assess synaptic density
• OTHER: UHR PET/CT scan of the brain with ¹⁸F-MK6240 — Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-MK6240 radiotracer to assess neurofibrillary tangles
• OTHER: 3T MRI imaging of the brain — All participants will undergo 3T MRI, including T1- and FLAIR-weighted sequences for anatomical reference and white matter pathology, neuromelanin-sensitive imaging to assess SN and LC integrity, and multi-shell diffusion-weighted imaging (DWI) for white matter tractography.

Primary Outcomes

• Volume distribution (mL/cm³) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240 (Through study completion, an average of 4 year)
• Standardized uptake value ratios (SUVR) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240 (Through study completion, an average of 4 year)

Secondary Outcomes

• Correlation between regional PET tracer uptake and cognitive performance (Through study completion, an average of 4 year)
• Correlation between regional PET tracer uptake and motor and functional impairment (Through study completion, an average of 4 year)

Full Eligibility Criteria

Inclusion Criteria:

* WP1: Healthy controls
* Age between 18 and 90 years old (15 aged 18-50 years and 25 aged 50 90 years);
* Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs and clinical laboratory tests;
* No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment;
* No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline;
* In subjects \< 60 years of age, a normal structural MRI scan as assessed by expert radiologist.
* In subjects \>= 60 years of age white matter hyperintensities corresponding to a WML (white matter lesion) score \<= 2 (of 3) on the Age-Related White Matter changes scale are acceptable;
* When older than 50 years of age, the volunteer is willing to undergo a p- tau217 blood sample.
* WP2: Dementia
* Patient has a clinical diagnosis of biomarker-proven prodromal AD
* WP3: ALS spectrum
* Subject must meet El Escorial Criteria (30) and Awaji-Shima criteria (31) for at least possible ALS;
* WP4: Movement disorders
* (all): Patient (or legal representative, when applicable) is able to understand the patient information form and give written informed consent.
* Parkinson´s disease (PD):
* Patient has clinically established PD based on the Movement Disorder Society (MDS) diagnostic criteria (32);
* Patient has an abnormal 18F-PE2I PET;
* No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline.
* Multiple system atrophy (MSA)
* Patient has clinically established or clinically probable MSA-P based on the
* Movement Disorder Society (MDS) diagnostic criteria (33);
* Patient has an abnormal 18F-PE2I PET.
* Progressive supranuclear palsy (PSP)
* Patient has an abnormal 18F-PE2I PET;
* Patient has clinically established probable PSP according to the latest MDS criteria
* Dementia with Lewy bodies (DLB)
* Patient has probable DLB by consensus criteria (cognitive impairment MoCA \< 26 + visual hallucinations and/or fluctuating alertness);
* Patient has an abnormal 18F-PE2I PET.
* Idiopathic REM sleep behavior disorder (iRBD)
* Patient has Polysomnography-confirmed iRBD;
* No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline;
* No clinical evidence of parkinsonism at baseline.
* WP5: Psychosis
* DSM 5 criteria for a non-affective schizophrenia spectrum psychotic disorder;
* Age between 18 and 55 years old for adult-onset psychosis, onset of psychosis (and age) above 60 years old for very late onset psychosis.

Exclusion Criteria:

* Subject has a history of any major (other) internal, psychiatric or neurological disease that may interfere with the investigations (especially liver and kidney disease, uncontrolled diabetes, cancer, severe depression, stroke, severe TBI);
* Subject is currently a user (including recreational use) of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse;
* Subject chronically uses medication that has central nervous system effects (e.g. strong painkillers such as opioids, neuroleptics,..; ) (other than prescribed for the illness in case of patients);
* Subject has had exposure to ionizing radiation (\> 1 mSv) in other research studies within the last 12 months;
* Subject has a contra-indication for MRI scanning;
* Subject suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures; subject cannot lie still for (at least) 60 minutes inside the scanner;
* (For subjects with arterial sampling): The subject is hypersensitive to lidocaine (used for local anaesthesia during the placement of the arterial catheter), has an abnormal Allen test (a test to check blood flow in the arteries of the forearm) or is on anti-coagulant therapy;
* Subject (or his/her legal representative) does not understand the study procedures;
* Subject is unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator;
* Subject is potentially pregnant (hCG test can be done if doubt exists).

Trial Locations

• UZ Leuven, Leuven, Vlaams-Brabant, Belgium

Frequently Asked Questions

Related Conditions

• Alzheimer Dementia (AD)
• Amyotrophic Lateral Sclerosis (ALS)
• Parkinson's Disease
• REM Sleep Behavior Disorder (iRBD)
• Progressive Supranuclear Palsy (PSP)
• Multiple System Atrophy (MSA)
• Dementia With Lewy Bodies (DLB)
• ALS With Frontotemporal Dementia (ALS/FTD)
• Adult Onset Psychotic Disorder
• Very Late Onset Psychotic Disorder

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