Tau PET Imaging for Frontotemporal Dementia

(SLD3 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Keith Josephs, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy

Disqualifiers: Traumatic brain injury, Strokes, Others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a drug called AV-1451 to study its ability to bind to tau proteins in the brains of patients with PPA and FTD. By doing this, researchers hope to better understand tau buildup in these conditions.

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.

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

18F-flortaucipir, also known as Tauvid, has been used in various studies for imaging tau protein in the brain, particularly in Alzheimer's disease. While the research primarily focuses on its effectiveness in detecting tau, it has been used safely in humans for these imaging purposes. ^{1 2 3 4 5}

How is the drug 18F-flortaucipir used in frontotemporal dementia different from other treatments?

18F-flortaucipir is unique because it is a PET imaging agent that specifically targets tau protein deposits in the brain, which are associated with cognitive impairments. Unlike other treatments that may focus on symptoms, this drug helps visualize tau pathology, aiding in the diagnosis and differentiation of frontotemporal dementia from other conditions like Alzheimer's disease. ^{1 2 4 6 7}

Research Team

Keith Josephs, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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)

Trial Timeline

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

Treatment Details

Interventions

• F-18 AV 1451 (Tau PET tracer)

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.

Participant Groups

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

All subjects will receive a Tau PET scan.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

Findings from Research

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 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 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 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 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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. [2021]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation. [2021]

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

Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography. [2023]