Tau PET Imaging for Primary Progressive Aphasia

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how tau, a protein linked to brain changes in diseases like Alzheimer's, accumulates in people with Primary Progressive Aphasia (PPA). Researchers use a special brain scan (PET scan) with a tracer called AV-1451 (also known as Flortaucipir or Tauvid) to map tau build-up. This could enhance understanding of PPA and potentially lead to new treatments. Suitable participants have PPA, a condition that affects language skills and communication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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 prior data suggests that this PET protocol is safe for mapping tau pathology in PPA patients?

Previous studies have used a substance called 18F-AV-1451, or Flortaucipir, to detect tau protein buildup in the brain. PET scans facilitate this detection and enhance understanding of brain diseases like Primary Progressive Aphasia. Research has shown that 18F-AV-1451 is generally safe for patients, with no major reports of serious side effects. However, as this is a Phase 1 study, the primary goal is to ensure the tracer's safety for humans. Researchers continue to monitor closely for any possible side effects. Any issues in earlier studies were rare. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for primary progressive aphasia focus on managing symptoms through speech therapy and medications that might help some cognitive functions. However, unlike these approaches, 18F-AV-1451 offers something different by using a PET imaging agent to visualize tau protein deposits in the brain. This is a significant leap because it targets the underlying pathology rather than just the symptoms, potentially allowing for earlier and more precise interventions. Researchers are excited because this could lead to better diagnosis and understanding of the disease progression, paving the way for more targeted treatments in the future.

What evidence suggests that this PET protocol is effective for mapping tau pathology in Primary Progressive Aphasia?

Research has shown that 18F-AV-1451, also known as Flortaucipir, holds promise for detecting tau protein buildup in the brain, which is linked to primary progressive aphasia (PPA). Studies have found that this compound effectively highlights brain areas with tau proteins. In this trial, participants will receive an injection of 18F-AV-1451 and undergo PET scanning to visualize tau-related changes. In PPA patients, increased uptake of 18F-AV-1451 was observed, suggesting it can help visualize tau-related changes. This is important because tau buildup is a key factor in the development and progression of PPA. While primarily used for imaging, accurately mapping tau buildup could lead to better diagnosis and understanding of the disease. ^{3 6 7 8 9}

Who Is on the Research Team?

Emily Rogalski, Ph.D.

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7060829/

Longitudinal Flortaucipir ([18F]AV-1451) PET Imaging in ... Elevated flortaucipir ([ 18 F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia.

2. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-019-0470-7

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia ... We performed 18F-flortaucipir imaging in patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia (nfvPPA) (n = ...

3. withpower.com withpower.com/trial/phase-1-frontotemporal-dementia-1-2016-44542

Tau PET Imaging for Primary Progressive Aphasia 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 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S001094521730429X

Tau-PET imaging with [18F]AV-1451 in primary ... In a recent longitudinal study, we observed that in some PPAOS patients, the apraxia of speech remained the most salient feature over an average duration of 7 ...

5. jnnp.bmj.com jnnp.bmj.com/content/89/10/1032

[18F]AV-1451 binding in vivo mirrors the expected ... Here, we test the properties of [18F]AV-1451 in semantic dementia, including the semantic variant of primary progressive aphasia (svPPA) and its non-dominant ...

6. jnnp.bmj.com jnnp.bmj.com/content/89/10/1024

Flortaucipir tau PET imaging in semantic variant primary ... We undertook this study to investigate the localisation and magnitude of the presumed tau Positron Emission Tomography (PET) tracer [ 18 F]Flortaucipir (FTP)

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5896771/

[18F]AV-1451 tau-PET and primary progressive aphasia Results. Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA and agrammatic-PPA.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9292954/

Rates of longitudinal change in 18F‐flortaucipir PET vary ... In atypical AD, 18 F‐flortaucipir uptake slowed or declined over time in areas with high baseline signal and older, more impaired individuals.

9. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2018.06.2268

IC‐P‐201: FLORTAUCIPIR IMAGING IN PRIMARY ... The primary goal of this study was to investigate the utility of Flortaucipir (aka AV1451) PET imaging for discriminating between patients ...