Tau PET Imaging for Frontotemporal Dementia

(SLD3 Trial)

Overseen By Sarah M Boland, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy

Disqualifiers: Traumatic brain injury, Strokes, 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 the presence of tau protein in the brains of individuals with Primary Progressive Aphasia (PPA) and Frontotemporal Dementia. Participants will undergo a specialized brain scan using a compound called F-18 AV 1451 (also known as Tauvid or Flortaucipir F-18) to help researchers measure tau levels. Ideal participants are those experiencing progressive issues with speech, language, or behavior and meet the criteria for PPA or Frontotemporal Dementia. Individuals with other conditions affecting speech and language or certain medical conditions that complicate brain imaging are not eligible. As an unphased trial, this study provides participants the chance to contribute to foundational research that could enhance understanding and lead to future treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot participate if you are on medications that might affect brain structure or metabolism, like chemotherapy.

What prior data suggests that this imaging technique is safe for patients with Frontotemporal Dementia?

Research shows that F-18 AV 1451, also known as flortaucipir, is used in PET scans to detect tau protein in the brain. Tau proteins are linked to Alzheimer's disease and other types of dementia. The FDA has approved this substance for imaging in Alzheimer's, indicating its general safety for patients with memory and thinking issues.

Studies have demonstrated that F-18 AV 1451 effectively attaches to tau proteins, enabling doctors to visualize these proteins in the brain through imaging. It has been used in various research settings, and patients typically tolerate it well. However, its safety for other conditions, such as chronic traumatic encephalopathy, remains unclear.

Since F-18 AV 1451 is already FDA-approved for Alzheimer's imaging, it is likely considered safe for similar conditions, though some risks may still exist. Patients should always discuss potential risks and benefits with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Tau PET Imaging with F-18 AV 1451 for frontotemporal dementia because it offers a new way to visualize tau protein deposits in the brain. Unlike current treatments that mainly focus on managing symptoms, this imaging technique aims to directly assess the presence and spread of tau protein, which is a key player in the disease's progression. By providing a clearer picture of tau accumulation, it could lead to earlier and more accurate diagnosis and help tailor treatments more effectively.

What evidence suggests that this Tau PET scan is effective for assessing tau burden in Frontotemporal Dementia?

Research has shown that F-18 AV 1451, also known as 18F-flortaucipir, is used in PET scans to detect tau protein buildup in the brain. In Alzheimer's disease, it accurately aligns with expected tau locations, aiding in diagnosis. However, in frontotemporal dementia (FTD), it is less precise. While it can detect tau, it may not always distinguish between tau-related and non-tau-related issues in FTD. Despite these challenges, it remains a valuable tool for understanding tau buildup, particularly in dementia research. In this trial, all participants will undergo a Tau PET scan using F-18 AV 1451 to further explore its utility in FTD. ^{2 4 6 7 8}

Who Is on the Research Team?

Keith Josephs, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults over 18 who primarily speak English and have progressive speech/language issues or behavior changes, fitting the criteria for Primary Progressive Aphasia or Frontotemporal Dementia. They need someone to independently assess their functioning but can't join if they have other illnesses causing similar symptoms, are pregnant/breastfeeding, mute/unintelligible speech, MRI contraindications like metal implants, severe claustrophobia, brain structure abnormalities or are on certain medications.

Inclusion Criteria

I am over 18 years old.

I am experiencing worsening problems with my speech, language, or behavior.

I have been diagnosed with Primary Progressive Aphasia or Frontotemporal Dementia.

Exclusion Criteria

I do not have any illnesses like brain injury or Alzheimer's that affect my speech.

Any subject who is mute or whose speech is unintelligible will be excluded

Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, etc.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism (e.g. chemotherapy)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive a Tau PET scan using F-18 AV 1451 to assess tau burden in the brain

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• F-18 AV 1451

Trial Overview

The study tests F-18 AV 1451's ability to detect tau protein in the brain which is linked with Primary Progressive Aphasia and Frontotemporal Dementia. It aims to understand the overall tau burden in patients' brains through PET scans.

How Is the Trial Designed?

Group I: Tau PET Scan, F-18 AV 1451 Experimental Treatment 1 Intervention

All subjects will receive a Tau PET scan.

Group II: Normal Controls Active Control 1 Intervention

Subjects from our NIH funded Mayo Clinic Study of Aging (U01 AG006786) who have completed the identical tau-PET protocol with AV-1451 and MRI and clinical protocols. These participants were not consented or enrolled in this study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

The use of [18F]PM-PBB3 tau PET imaging successfully identified tau deposition in a patient with frontotemporal dementia (FTD) caused by a MAPT mutation, indicating its potential as a diagnostic tool for this condition.

In a comparison of tau PET tracers, [18F]PM-PBB3 showed positive retention in all patients with both 3-repeat and 4-repeat tau, while AV-1451 was less consistent, highlighting [18F]PM-PBB3's broader utility in detecting tau strains associated with FTD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation. Su, Y., Fu, J., Yu, J., 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 of 143 participants with confirmed frontotemporal lobar degeneration (FTLD) and varying levels of Alzheimer disease neuropathologic changes (ADNC), FTLD showed significantly higher baseline flortaucipir PET uptake in specific brain regions compared to both high and low ADNC cases.

The study found that baseline flortaucipir uptake was more effective than longitudinal changes in differentiating FTLD from ADNC, with a specific midbrain/inferior temporal uptake ratio providing excellent sensitivity (94%) and specificity (95%) for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography. Josephs, KA., Tosakulwong, N., Gatto, RG., 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]

In a study of 45 patients with various frontotemporal dementia (FTD) syndromes, 18F-flortaucipir PET imaging showed some elevated tau binding in specific brain regions, particularly in patients with nonfluent variant primary progressive aphasia (nfvPPA) and corticobasal syndrome (CBS).

However, the overall sensitivity and specificity of 18F-flortaucipir for detecting tau aggregates in FTD were limited, indicating a need for further research and the development of more specific imaging agents for FTD-related tau pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. Tsai, RM., Bejanin, A., Lesman-Segev, O., et al.[2021]

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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6357510/

18F-flortaucipir (AV-1451) tau PET in frontotemporal ...

In vivo, 18F-flortaucipir retention in Alzheimer's disease matches the expected distribution of tau pathology in Alzheimer's disease, ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30704514/

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia ...

18 F-flortaucipir in patients with FTD and predicted tauopathy or TDP-43 pathology demonstrated limited sensitivity and specificity.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02676843

Tau PET Imaging With 18F-AV-1451 in Subjects ...

Up to three 18F-AV-1451 scans will be performed (one per year) on control subjects without MAPT mutations, presymptomatic mutation carriers, and symptomatic ...

4.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1002/ana.24517

Validating novel tau positron emission tomography tracer ...

Results. Our data suggest that [F-18]-AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer brains ...

5.

mdpi.com

mdpi.com/1424-8247/14/2/110

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

These PET tracers have greatly impacted the diagnosis of AD patients in the clinic and can assist in evaluating patients with cognitive impairment and dementia.

6.

pmc.ncbi.nlm.nih.gov

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

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

These PET tracers have greatly impacted the diagnosis of AD patients in the clinic and can assist in evaluating patients with cognitive impairment and dementia.

7.

go.drugbank.com

go.drugbank.com/drugs/DB14914

Flortaucipir F-18: Uses, Interactions, Mechanism of Action

The safety and efficacy of flortaucipir F-18 in patients being evaluated for chronic traumatic encephalopathy are unknown and hence is not recommended.

8.

jamanetwork.com

jamanetwork.com/journals/jamaneurology/fullarticle/2764329

Positron Emission Tomography Imaging With [18F] ...

Findings from this study suggest that visual reads of [ 18 F]flortaucipir PET scans may accurately support a pathological diagnosis of Alzheimer disease.