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

Trial Summary

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 data supports the effectiveness of the drug 18F-flortaucipir (also known as 18F-AV-1451 or Tauvid) in neurodegenerative diseases?

Research shows that 18F-flortaucipir is effective in visualizing tau protein buildup in the brain, which is linked to Alzheimer's disease. It helps track changes in tau levels over time, especially in patients with cognitive impairment, providing valuable insights into disease progression. ^{1 2 3 4 5}

Is 18F-flortaucipir (Tauvid) safe for use in humans?

18F-flortaucipir (also known as Tauvid) is a PET imaging agent used to visualize tau protein in the brain, primarily for Alzheimer's disease. It has been used in various studies with participants, including those with Alzheimer's, mild cognitive impairment, and other neurodegenerative conditions, without specific safety concerns reported in the provided research articles. ^{1 2 3 4 6}

How is the drug 18F-flortaucipir unique in treating neurodegenerative diseases?

18F-flortaucipir is unique because it is a PET imaging agent specifically designed to bind to tau proteins in the brain, which are associated with Alzheimer's disease. Unlike other treatments that may target symptoms or other aspects of neurodegenerative diseases, this drug helps visualize and measure tau protein deposits, providing a clearer picture of the disease's progression. ^{1 3 5 6 7}

What is the purpose of this trial?

The purpose of this study is to measure the amount of a protein in the brain known as tau using an imaging procedure called Positron Emission Tomography (PET/CT). Tau has been shown to build up in the brains of patients with injury to brain cells. This study looks at neurodegenerative diseases such as frontotemporal degeneration (FTD).

Research Team

David Irwin

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer's disease dementia. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Parametric methods for [18F]flortaucipir PET. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Tau positron emission tomography imaging in C9orf72 repeat expansion carriers. [2020]

5. Germany pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948. [2021]

6. United States 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. [2022]

7. United States 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. [2023]