Diagnostic Imaging for Tauopathies

Overseen By Refatun Momo

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Pregnancy, Schizophrenia, Bipolar, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

94 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve how doctors diagnose certain brain conditions, such as Parkinson's Disease (PD), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and Frontotemporal Dementia (FTD). The study will use special brain scans, including Amyloid PET scans (a type of positron emission tomography) and MRI, to identify patterns or markers related to these diseases. Individuals diagnosed with PD, MSA, PSP, FTD, or healthy individuals willing to assist with research may be suitable participants. Participants should feel comfortable undergoing brain scans and be willing to consent to study procedures. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance diagnostic methods for these complex conditions.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications. It is best to discuss this with the study team or your doctor.

What prior data suggests that this protocol is safe?

Research has shown that Amyloid PET scans are generally safe. The FDA has approved these scans for diagnosing Alzheimer's disease, as they allow doctors to see amyloid plaques in the brain, which are linked to certain brain conditions. The scan is non-invasive but uses a small amount of radioactive material, which is usually well-tolerated with few reported side effects.

Studies indicate that brain MRI scans are also safe and commonly used in both medical practice and research. MRI scans use magnetic fields and radio waves to create detailed images of the brain and are non-invasive. They do not involve radiation, making them very safe. Some people might feel uncomfortable in the machine or experience minor side effects like dizziness, but these effects are usually temporary.

Neurologic exams, which assess brain and nervous system function, are safe and routine. They involve simple tests like checking reflexes and coordination and do not carry risks or side effects.

Overall, the procedures in this trial, including Amyloid PET scans, brain MRI scans, and neurologic exams, have a strong safety record. Participants should feel reassured about the low risk of serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the diagnostic imaging methods being explored for tauopathies because they offer a more comprehensive way to understand these complex brain conditions. Unlike traditional approaches that might focus on symptoms alone, these methods include amyloid PET scans and brain MRI scans, which can provide detailed images of brain structures and amyloid deposits associated with tauopathies. These imaging techniques could potentially lead to earlier and more accurate diagnoses, allowing for more targeted and effective intervention strategies. By using advanced imaging to assess brain changes, researchers hope to pave the way for better treatment options in the future.

What evidence suggests that these diagnostic assessments are effective for tauopathies?

Research has shown that Amyloid PET scans, which participants in this trial may undergo, can successfully detect amyloid plaques in the brain, often associated with conditions like Parkinson's Disease, Multiple System Atrophy, Progressive Supranuclear Palsy, and Frontotemporal Dementia. These plaques are linked to these diseases, and studies have demonstrated that PET imaging reliably detects them. Participants may also receive Brain MRI scans, which provide detailed images of the brain's structure, helping to identify changes related to neurodegenerative diseases. Additionally, neurologic exams, another component of this trial, assess nervous system function, offering valuable insights into how these diseases affect movement and brain function. Together, these tests provide a comprehensive view of brain health and the presence of disease. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-85 with Parkinson's Disease, Multiple System Atrophy, Progressive Supranuclear Palsy, Frontotemporal Dementia or healthy controls. They must understand the study and consent to participate. Pregnant women and those with major psychiatric disorders or substance abuse issues are excluded.

Inclusion Criteria

Participants must be willing to participate in the study in accordance with institutional and federal guidelines

Participants must be informed of the investigational nature of the study and be willing to provide written informed consent

A group of experts will decide if you have a specific brain condition (PD, MSA, PSP, FTD) or if you are a healthy control.

Exclusion Criteria

You have a serious mental illness like schizophrenia or bipolar disorder.

Contraindications or inability to tolerate imaging, arterial line or IV placement or blood draw procedures in the opinion of an investigator or treating physician

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Assessment

Subjects may receive a brain MRI and neurological exam with diagnostic assessments

8 weeks

Multiple visits for imaging and assessments

Follow-up

Participants are monitored for safety and effectiveness after diagnostic assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amyloid PET scan
• Brain MRI Scan
• Neurologic exam

Trial Overview The trial tests new radiotracers' specificity using diagnostic assessments like neurologic exams and brain scans (Amyloid PET and MRI) across multiple sites including U Penn, Pitt, Yale University, UCSF, and WU.

How Is the Trial Designed?

Group I: Diagnostic Assessments Experimental Treatment 2 Interventions

Subjects may receive a brain MRI and neurological exam with diagnostic assessments.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Current imaging techniques, such as PET and MRI, can help identify different subtypes of Alzheimer's disease (AD) and differentiate them from other neurodegenerative diseases, potentially at an early stage.

While amyloid PET is useful for early detection of AD, it does not differentiate between subtypes; however, tau and glucose PET, along with MRI, can reveal specific patterns of pathology associated with different AD subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Clinical Subtypes and Associated Brain Networks in Alzheimer's Disease. Herholz, K.[2022]

Amyloid PET imaging is a valuable tool for the early and accurate diagnosis of Alzheimer's disease by evaluating the amyloid-β pathology, which is a key biomarker for the disease.

The article emphasizes the importance of proper administration, scanning techniques, and image analysis methods for amyloid PET, aiming to enhance its reliability in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia. Akamatsu, G., Ohnishi, A., Aita, K., et al.[2017]

In a phase 1b trial involving 278 patients with early stages of Alzheimer's disease, amyloid PET imaging successfully identified 61% of patients as amyloid-positive, making it a promising tool for selecting participants for clinical trials.

The study found that ApoE ε4 carriers were more likely to be amyloid-positive (80%) compared to noncarriers (43%), highlighting the potential of PET imaging to enrich trial populations based on genetic risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial. Sevigny, J., Suhy, J., Chiao, P., et al.[2022]

Human amyloid imaging has advanced significantly, starting from the use of Thioflavin T derivatives as PET tracers to the FDA approval of Florbetapir in 2012, which allows for in vivo diagnosis of Alzheimer's disease (AD).

While amyloid PET imaging is a promising tool for detecting β-amyloid pathology in the brain, it is important to note that it serves as a surrogate marker and does not directly diagnose Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid imaging: the court of public opinion. Lerner, AJ.[2018]

Amyloid PET imaging can lead to significant changes in the diagnosis of Alzheimer's disease, with a pooled estimate showing a 31% change rate across 16 studies involving various patient populations.

The imaging technique also increases diagnostic confidence and influences patient management decisions, particularly in cases where there is high diagnostic uncertainty, affecting treatment plans for Alzheimer's medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice. Kim, Y., Rosenberg, P., Oh, E.[2019]

Amyloid PET (aPET) imaging led to a revision of diagnoses in 31.3% of cases among cognitively impaired subjects, significantly higher than the 3.2% revision rate in control patients with delayed feedback, indicating its strong impact on diagnostic accuracy.

Following aPET, 62.1% of patients experienced increased diagnostic confidence, and 72.2% had changes in management plans, highlighting its effectiveness in improving patient care and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Aggregated Analysis on the Impact of Amyloid PET Brain Imaging on the Diagnosis, Diagnostic Confidence, and Management of Patients being Evaluated for Alzheimer's Disease. Fantoni, ER., Chalkidou, A., O' Brien, JT., et al.[2023]

Recent advances in amyloid PET imaging have improved the ability to diagnose Alzheimer's disease and related dementias, providing valuable insights into brain structure and function.

Current guidelines recommend the use of amyloid PET imaging for patients with cognitive complaints, highlighting its potential clinical value in early detection and management of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Neuroimaging in the Assessment of the Cognitively Impaired Elderly. Kollack-Walker, S., Liu, CY., Fleisher, AS.[2018]

Amyloid imaging, particularly using Pittsburgh Compound-B (PIB) with PET scans, is a highly sensitive method for detecting amyloid-beta accumulation in the brain, which can serve as an early biomarker for Alzheimer's disease (AD).

This imaging technique not only aids in the early diagnosis of AD but also helps monitor the effectiveness of treatments aimed at reducing amyloid-beta levels, and can differentiate AD from other neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Amyloid imaging]. Ishii, K.[2016]

Amyloid imaging is a non-invasive method that allows researchers to see how amyloid beta builds up in the brains of living people, which is crucial for studying early Alzheimer's disease.

This imaging technique has become essential for both observational and interventional studies of Alzheimer's, especially as new disease-modifying drugs are developed, although its current clinical use is mainly for diagnosing atypical dementia cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Amyloid imaging]. Ishii, K.[2016]

Recent advancements in positron emission tomography (PET) allow for the in vivo detection of beta-amyloid (Aβ) pathology, with fluorine-18 labeled radiopharmaceuticals becoming the preferred choice over carbon-11 labeled Pittsburgh compound B for clinical use.

Amyloid imaging is recommended for evaluating patients with mild cognitive impairment or atypical dementia, but its use in asymptomatic individuals is currently discouraged due to uncertainty in prognosis, despite the potential for elevated Aβ levels to indicate preclinical Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of amyloid PET across the spectrum of Alzheimer's disease: clinical utility and associated ethical issues. Leuzy, A., Zimmer, ER., Heurling, K., et al.[2020]

Human amyloid imaging using PET scans allows for the detection of early cerebral amyloidosis, a key feature of Alzheimer's disease, potentially leading to earlier diagnosis.

While initial data is promising, it is important to interpret amyloid PET results carefully, as the presence of amyloidosis does not necessarily indicate clinical Alzheimer's disease or predict immediate cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid imaging of Alzheimer's disease using Pittsburgh Compound B. Johnson, KA.[2019]

A systematic review of 10 papers from 7 studies found that disclosing amyloid PET scan results generally did not lead to increased depression among individuals with cognitive impairment, but those with mild cognitive impairment and high amyloid levels experienced more distress or anxiety.

While participants remembered their scan results, it remains uncertain if this improved their understanding of their diagnosis, indicating a need for further research on the psychosocial impacts of amyloid PET scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychosocial and Behavioral Outcomes for Persons With Cognitive Impairment and Caregivers Following Amyloid-β PET Scan Disclosure: A Systematic Review. Couch, E., Ashford, MT., Zhang, W., et al.[2023]

Citations

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Updated Appropriate Use Criteria for Amyloid and Tau PET A multidisciplinary workgroup to update appropriate use criteria (AUC) for amyloid positron emission tomography (PET) and to develop AUC for tau PET.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9074832/

Amyloid and Tau Positron Emission Tomography Imaging in ... This review aims to provide an overview of the existing Aβ and tau PET imaging biomarkers and their binding properties from in silico, in vitro, and in vivo ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724002012

Diagnostic Biomarkers of Amyloid and Tau Pathology in ... We provide an overview of the diagnostic biomarkers for amyloid and tau pathology that are currently available in the US and/or EU for clinical use.

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14338

Updated appropriate use criteria for amyloid and tau PET: A ... Positron emission tomography with the radiolabeled glucose analog 18F-fluorodeoxyglucose (FDG) has been used to image regional cerebral glucose ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10432878/

Tau as a diagnostic instrument in clinical trials to predict ... These findings suggest that a positive tau PET scan is associated (≥93%) with amyloid positivity in individuals with early symptomatic AD, with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4498486/

Amyloid imaging, risk disclosure and Alzheimer's disease Amyloid neuroimaging is now approved by the US FDA to aid in the diagnosis of AD, and is being used to identify amyloid-positive but asymptomatic individuals.

7. nature.com nature.com/articles/s41593-025-02000-6

Tau PET positivity in individuals with and without cognitive ... Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated ...