Tau PET Imaging for Neurodegenerative Disease

Overseen By Dahlia Kamel

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Pennsylvania

Must not be taking: Psychoactive medications

Disqualifiers: Pregnancy, Cardiovascular disease, Psychiatric conditions, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a protein called tau in the brain, which tends to accumulate in people with certain neurodegenerative diseases, using a special imaging technique known as PET/CT. The study focuses on conditions like Alzheimer's, Parkinson's, and several others affecting the brain. Researchers use a radiotracer called 18F-AV-1451 (also known as Flortaucipir or Tauvid) to visualize tau protein accumulation. The trial seeks participants diagnosed with one of these diseases or healthy individuals for comparison. Participants should receive care at specific clinics and be open to undergoing imaging procedures.

As a Phase 2, Phase 3 trial, this study measures how well the treatment works in an initial group and is in the final step before FDA approval, offering participants a chance to contribute to crucial advancements in neurodegenerative disease research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are a healthy control subject, you cannot use psychoactive medications or substances.

What prior data suggests that this imaging procedure is safe for measuring tau in neurodegenerative diseases?

Research has shown that 18F-AV-1451, also known as Tauvid, is safe for use in clinical trials. The FDA has approved Tauvid for PET scans in individuals with memory and thinking problems, indicating its general safety for imaging. Studies have found that it effectively targets tau proteins in the brain, which are linked to diseases like Alzheimer's.

For [18F]T807, early research suggests it is a promising tool for detecting tau buildup in the brain. Although there is less direct safety information available, its inclusion in several clinical trials indicates it has passed initial safety checks. Both tracers are used for imaging, not as treatments, which typically means they carry fewer risks. It is important to consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Tau PET Imaging technique because it offers a new way to visualize and understand tau protein buildup in neurodegenerative diseases like Alzheimer's and Parkinson's. Unlike traditional diagnostic methods that rely on observing symptoms or using MRI scans, Tau PET Imaging uses radiotracers like 18F-AV-1451 and [18F]T807 to specifically target and highlight tau proteins in the brain. This targeted approach could lead to earlier and more accurate diagnoses, potentially transforming how these conditions are managed and paving the way for more effective treatments in the future.

What evidence suggests that this imaging procedure is effective for measuring tau in neurodegenerative diseases?

Research has shown that 18F-AV-1451, also known as flortaucipir, effectively detects the buildup of tau proteins in the brain. These proteins often clump together in individuals with Alzheimer's disease and other brain disorders. In this trial, participants will undergo imaging with 18F-AV-1451 to visualize tau pathology. Similarly, [18F]T807, another imaging agent under study in this trial, has shown promise due to its strong binding to tau proteins and effectiveness in visualizing them. Both agents help identify brain changes related to tau, which is crucial for diagnosing and understanding diseases like Alzheimer's. This makes them valuable tools for studying and managing brain diseases. ^{2 3 6 7 8}

Who Is on the Research Team?

David Irwin

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with neurodegenerative diseases like FTD, Alzheimer's, Parkinson's, and others. Participants must be able to give informed consent themselves or through a legal representative and follow the study schedule. A recent brain MRI is required; if not available, one will be provided as part of the study.

Inclusion Criteria

I have been diagnosed with a specific neurodegenerative condition.

A brain MRI is required to participate in this study. If a brain MRI has been performed within 6 months prior to enrollment in this study and is of research quality, that scan may be used for the study analysis. Subjects who do not have a brain MRI will undergo a brain MRI as part of one of the Center's other ongoing study protocols.

Participants must be willing and able to comply with scheduled visits and imaging procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET/CT imaging to measure tau protein in the brain using 18F-AV-1451

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for changes in neuropsychological and MRI measures over time

10 years

What Are the Treatments Tested in This Trial?

Interventions

• 18F-AV-1451
• [18F]T807

Trial Overview

The trial tests an imaging agent called 18F-AV-1451 using PET/CT scans to measure tau protein levels in the brain, which are linked to cell damage in various neurodegenerative diseases.

How Is the Trial Designed?

Group I: Positron Emission Tomography (PET/CT) Imaging of Tau Pathology in Neurodegenerative Disease Experimental Treatment 1 Intervention

Individuals who have been diagnosed with FTD, PPA, CBD, PSP, MCI, AD, PCA, PD, PDD, DLB, MSA, ALS or FTD-ALS may participate in this study if they are 18 years of age or older; most participants will be receiving care at the clinical practices of the of the University of Pennsylvania and at Pennsylvania Hospital Department of Neurology. Healthy control subjects will also be recruited for this study.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Avid Radiopharmaceuticals

Industry Sponsor

Trials

66

Recruited

9,700+

Dr. Daniel M. Skovronsky

Avid Radiopharmaceuticals

Chief Executive Officer since 2004

MD and PhD in Neuroscience from the University of Pennsylvania

Dr. Adam S. Fleisher

Avid Radiopharmaceuticals

Chief Medical Officer since 2022

MD, MAS

Published Research Related to This Trial

In a study involving 202 participants aged 50 and older, flortaucipir PET imaging revealed a significant increase in tau burden over 18 months in individuals with amyloid-β, indicating a relationship between tau accumulation and cognitive decline in Alzheimer's disease.

The study found that both the initial tau levels and the changes in tau burden were strongly associated with cognitive performance, suggesting that monitoring tau levels could help predict cognitive deterioration in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia. Pontecorvo, MJ., Devous, MD., Kennedy, I., et al.[2022]

In a study involving 33 patients with progressive supranuclear palsy (PSP), 18 F-flortaucipir showed significantly elevated uptake in specific brain regions compared to normal controls (46 participants) and patients with Parkinson disease (26 participants), indicating its potential as a biomarker for tau pathology in PSP.

The globus pallidus region was particularly effective in distinguishing PSP patients from both controls and Parkinson disease patients, with high accuracy (AUC values of 0.872 and 0.893, respectively), suggesting that 18 F-flortaucipir could aid in the diagnosis of PSP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study. Schonhaut, DR., McMillan, CT., Spina, S., et al.[2022]

In a study involving 25 participants (18 with Alzheimer's disease, 3 with mild cognitive impairment, and 4 healthy controls), the novel tau PET tracer [18F]RO948 demonstrated higher retention in the entorhinal cortex and lower off-target binding in other brain regions compared to [18F]flortaucipir.

Both tracers showed comparable binding in neocortical regions, but [18F]RO948's reduced off-target binding and stable retention over time suggest it may provide more accurate diagnostic information for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948. Smith, R., Schöll, M., Leuzy, A., et al.[2021]

The study evaluated the effectiveness of different methods for generating parametric images of the PET tau tracer [18F]flortaucipir in 20 participants (10 Alzheimer's disease patients and 10 controls), finding that both Regional Parametric Modeling (RPM) and Spectral Analysis (SA) produced results comparable to traditional non-linear regression methods.

While the Standardized Uptake Value ratio (SUVr) showed good correlation with other methods, it exhibited bias that varied with uptake time and binding levels, indicating the need for further investigation with larger datasets to fully understand its implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parametric methods for [18F]flortaucipir PET. Golla, SS., Wolters, EE., Timmers, T., et al.[2023]

The FDA-approved radiotracer 18F-flortaucipir is increasingly used in PET imaging to visualize tau pathology in patients with cognitive impairment, particularly Alzheimer's disease.

An international consensus has been established to standardize the procedural use of 18F-flortaucipir PET imaging, which will enhance its application in clinical practice for diagnosing and managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. Tian, M., Civelek, AC., Carrio, I., et al.[2022]

C9orf72 expansion carriers showed increased tau accumulation in the entorhinal cortex as measured by AV-1451 PET imaging, indicating a potential link to primary age-related tauopathy.

Despite the increased tau uptake, there was no correlation between AV-1451 accumulation and clinical severity, disease duration, or cognitive performance in the studied individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau positron emission tomography imaging in C9orf72 repeat expansion carriers. Ly, CV., Koenig, L., Christensen, J., et al.[2020]

Flortaucipir PET imaging shows a strong correlation with tau burden in Alzheimer's disease (AD), indicating its effectiveness in evaluating tau levels in AD patients, although there are exceptions where the uptake does not match due to other conditions.

In contrast, flortaucipir has limited effectiveness in assessing tau burden in non-Alzheimer's tauopathies, suggesting a need for improved imaging techniques to better detect tau in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of regional tau distribution by Tau-PET and Post-mortem neuropathology in a representative set of Alzheimer's & frontotemporal lobar degeneration patients. Gatto, RG., Carlos, AF., Reichard, RR., et al.[2023]

Citations

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We developed a novel 18 F-flortaucipir PET (FTP, or Tauvid) visual read method enabling stratification of patients with Alzheimer disease (AD) according to the ...

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If 18F-AV1451 exhibits offtarget binding, its ability to accurately differentiate AD from other neurodegenerative conditions becomes uncertain. ...

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Further, it appears that [18F]AV-1451 is sensitive to the regional distribution of tau deposition in different stages of PPAOS, given the relationship between ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7911942/

Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau ...

Tauvid has high selectivity towards tau over Aβ and is safe to be used in the clinical trials. Tauvid PET imaging can distinguish late-stage AD from cognitively ...

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Discriminative Accuracy of [ 18 F]flortaucipir Positron ...

The use of [ 18 F]flortaucipir PET had an estimated sensitivity of 89.9% and specificity of 90.6% for Alzheimer disease vs other neurodegenerative diseases.

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Quantitative Evaluation of [18F]T807 as a Potential PET ...

Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... Kinetic Modeling of the Tau PET Tracer 18F-AV-1451 in Human Healthy Volunteers and ...