Tau PET Imaging for Primary Progressive Aphasia

Recruiting at 1 trial location

Overseen By Seyi Adeolu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Disqualifiers: Pregnancy, Breastfeeding, Radiation, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

70 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to see if a PET scan with a special tracer can map harmful protein build-up in the brains of people with language problems due to Primary Progressive Aphasia.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug 18F-AV-1451 (Flortaucipir, Tauvid, 18F-T807) for primary progressive aphasia?

The drug 18F-AV-1451, also known as Flortaucipir, is primarily used to detect tau protein build-up in the brain, which is common in Alzheimer's disease. While it shows strong links to tau burden in Alzheimer's patients, its effectiveness in detecting tau in non-Alzheimer's conditions like primary progressive aphasia is limited, although some regional associations have been observed. ^{1 2 3 4 5}

Is 18F-flortaucipir (also known as 18F-AV-1451, Flortaucipir, Tauvid, 18F-T807) safe for use in humans?

18F-flortaucipir has been used in various studies for imaging tau protein in the brain, particularly in Alzheimer's disease and other cognitive impairments. While these studies focus on its effectiveness in detecting tau, they do not report significant safety concerns, suggesting it is generally safe for use in humans. ^{1 3 5 6 7}

How does the drug 18F-flortaucipir differ from other treatments for primary progressive aphasia?

18F-flortaucipir is unique because it is a PET imaging agent that helps visualize tau protein deposits in the brain, which is not a standard treatment but a diagnostic tool to understand the disease better. Unlike other treatments that may focus on symptom management, this drug provides insights into the underlying pathology of primary progressive aphasia by highlighting tau accumulation patterns. ^{1 3 4 6 8}

Research Team

Emily Rogalski, Ph.D.

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for individuals with Primary Progressive Aphasia and other related dementias. Participants must not be pregnant, breastfeeding, or undergoing clinical radiation treatments.

Inclusion Criteria

You must have primary progressive aphasia.

Exclusion Criteria

Pregnancy

Breastfeeding

Currently undergoing radiation treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive an injection of 10 Mci of AV-1451 and undergo PET scanning for brain imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for tau deposition levels using standardized uptake value ratio (SUVR) in cortical and medial temporal regions

2 years

Treatment Details

Interventions

• 18F-AV-1451

Trial Overview The study aims to map tau protein build-up in the brain using a PET scan with a tracer called AV-1451. It will document where and how much tau protein is present in patients with Primary Progressive Aphasia.

Participant Groups

Group I: AV-1451 Recipients Experimental Treatment 2 Interventions

Participants in this arm of the study will all receive an injection of 10 Mci of AV-1451 and then be scanned in a PET scanner for brain imaging.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a study involving seven patients with semantic variant primary progressive aphasia (svPPA) and 20 controls, all patients showed elevated uptake of the tau PET tracer [18F]Flortaucipir in the anterior temporal lobe, indicating potential tau pathology despite the typical association of svPPA with TDP-43 pathology.

The elevated tracer signal correlated with areas of brain atrophy, suggesting that the tracer may bind to non-tau molecules related to neurodegeneration, highlighting the need for further research to clarify its binding targets in FTLD-TDP cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. Makaretz, SJ., Quimby, M., Collins, J., et al.[2021]

This study found a strong correlation (Pearson r = 0.81) between flortaucipir PET imaging results and levels of abnormally phosphorylated tau (Ptau) in brain tissue from patients with dementia, suggesting that flortaucipir can effectively reflect tau pathology in Alzheimer's disease.

The research indicates that while flortaucipir PET correlates well with Ptau levels, it does not show a significant relationship with amyloid-β (Aβ1-42), highlighting its potential specificity for tau-related changes in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. Pontecorvo, MJ., Keene, CD., Beach, TG., et al.[2021]

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]

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]

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 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]

References

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

Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. [2021]

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

18F-flortaucipir uptake patterns in clinical subtypes of primary progressive aphasia. [2019]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

7. 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]

8. 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]