Tau PET Imaging for Alzheimer's Disease

(AV1451 ADC Trial)

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Severe dementia, MRI/PET contraindication, 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

160 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study coordinators or your doctor.

What data supports the effectiveness of the drug Flortaucipir F 18 (Tauvid) for Alzheimer's disease?

Research shows that Flortaucipir F 18 PET scans can effectively measure tau protein buildup in the brain, which is linked to Alzheimer's disease. This drug helps doctors see how much tau is present, which can indicate the progression of the disease and help in planning treatment. ^{1 2 3 4 5}

Is Tau PET Imaging with Flortaucipir F 18 safe for humans?

Flortaucipir F 18, used in PET imaging for Alzheimer's disease, has been approved by the FDA, indicating it has met safety standards for human use. It has been used in studies with participants having normal aging, mild cognitive impairment, and Alzheimer's disease without significant safety concerns reported. ^{1 2 3 5 6}

How does the drug 18F-flortaucipir differ from other Alzheimer's treatments?

18F-flortaucipir is unique because it is a PET imaging agent specifically designed to detect tau protein deposits in the brain, which are a hallmark of Alzheimer's disease. Unlike other treatments that may focus on symptoms or other aspects of the disease, this drug helps visualize and assess the extent of tau pathology, aiding in diagnosis and research. ^{1 4 7 8 9}

What is the purpose of this trial?

The primary objective of this study is to measure the concentration and the regional brain distribution of pathologic tau deposition using the PET tracer AV-1451 in participants in the UAB-ADC cohort. The amount and distribution of AV-1451 in the brain will be correlated to demographic, clinical, genetic, and biospecimen data acquired through the separate ongoing UAB-ADC study. Assessment of interactions between race and vascular risk factors, brain tau levels measured with AV-1451-PET, and cognitive status will be the primary outcome of this imaging study. Individuals participating in this AV-1451-PET/MRI study will also be enrolled in an ongoing \[C-11\]PiB-PET/MRI study (IRB-300001005, IND-138128), and their amyloid, tau and cognitive statuses will be compared in terms of race and vascular risk factors.

Eligibility Criteria

This trial is for individuals already enrolled in the UAB-ADC study, focusing on Alzheimer's Disease. Participants must also be part of an amyloid-PET substudy but don't need to have completed it. Women capable of childbearing must test negative for pregnancy. Those with severe dementia or conditions preventing MRI/PET scans cannot join.

Inclusion Criteria

You are currently participating in a different research study about amyloid-PET at UAB-ADC.

I am not pregnant or have been menopausal for over a year or am surgically sterilized.

You are a UAB-ADC study participant.\n

Exclusion Criteria

You cannot have an MRI or PET scan for medical reasons.

Meets any exclusion criteria for the UAB-ADC study

Inability to participate in the imaging studies due to severity of dementia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo tau-PET imaging using the tracer [F-18]AV-1451 with a simultaneous PET/MRI system

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

5 years

Treatment Details

Interventions

• [F-18]AV-1451-PET

Trial Overview [F-18]AV-1451-PET imaging is being tested to measure and map tau protein deposits in the brain, which are linked to Alzheimer's. The results will be analyzed alongside demographic, clinical, genetic data from the UAB-ADC cohort to understand how race and vascular risks affect cognitive status.

Participant Groups

Group I: [F-18]AV-1451-PET/MRI Experimental Treatment 1 Intervention

All participants in this study will undergo a tau-PET imaging using the tracer \[F-18\]AV-1451 with a simultaneous PET/MRI system. The \[F-18\]AV-1451 dosage is 740MBq (10 mCi) given intravenously, and the PET/MRI imaging will occur 75-105 min after tracer injection.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

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]

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]

Flortaucipir PET scans can effectively predict near-term clinical progression in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), with 70% of those showing an advanced AD pattern experiencing significant clinical deterioration over 18 months.

The study involved 364 participants, and those with an advanced AD pattern had a higher risk of clinical decline compared to those with a nonadvanced pattern, indicating that these scans can provide valuable prognostic information for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. Lu, M., Pontecorvo, MJ., Devous, MD., 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]

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]

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]

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 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]

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

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

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

Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease: Results From 2 Phase III Clinical Trials. [2022]

4. 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]

5. 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]

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. England pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

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