Tau Tracer Comparison for Alzheimer's Disease

(HEAD Trial)

Recruiting at 9 trial locations

Overseen By Firoza Z Lussier, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1

Sponsor: Tharick Pascoal

Disqualifiers: Pregnant, Breastfeeding, Cognitive impairment, others

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

Compensation: Varies

Number of Visits: 2

620 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial uses special imaging agents to help visualize harmful brain proteins in people at risk of Alzheimer's disease. The agents make these proteins glow during scans, allowing doctors to see them clearly and monitor the disease.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if any medication could increase risk, limit tolerance, or interfere with the study, you might need to stop taking it. This decision will be made by the investigator.

Is 18F-Flortaucipir safe for human use?

18F-Flortaucipir is an FDA-approved diagnostic agent for PET imaging in Alzheimer's disease, and quality control tests have shown it meets all specifications for human use, indicating it is generally safe. ^{1 2 3 4 5}

What makes the drug 18F-Flortaucipir unique for Alzheimer's disease?

18F-Flortaucipir is unique because it is a PET imaging agent specifically designed to target and visualize tau protein deposits in the brain, which are a hallmark of Alzheimer's disease. This allows for a more precise diagnosis and understanding of the disease progression compared to other treatments that do not specifically target tau. ^{1 2 3 4 6}

What data supports the effectiveness of the drug 18F-Flortaucipir in Alzheimer's disease?

Research shows that 18F-Flortaucipir is effective in identifying tau protein buildup in the brain, which is linked to Alzheimer's disease. It has been shown to accurately detect tau in patients, helping to understand the progression of the disease. ^{1 2 3 5 6}

Who Is on the Research Team?

Tharick Pascoal, MD PhD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for people aged 50-90 with no cognitive impairment, mild cognitive impairment, or Alzheimer's disease. They must be able to undergo repeated MR/PET imaging and have someone who can report on their functioning. Pregnant women and those unable to consent or at increased risk due to other conditions/medications are excluded.

Inclusion Criteria

You are willing and able to have multiple MRI/PET scans done.

You have an informant who will be able to provide an independent evaluation of functioning.

I am willing and able to have multiple MR/PET scans.

Exclusion Criteria

Compensation Provided

I have been diagnosed with Alzheimer's Disease.

Conducted in Providence, RI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline PET scans with Flortaucipir and MK-6240, amyloid-β PET scan, MRI, cognitive tests, and blood draw for biomarkers

1-2 weeks

1 visit (in-person)

Follow-up Assessment

Participants undergo follow-up PET scans with Flortaucipir and MK-6240, amyloid-β PET scan, MRI, cognitive tests, and blood draw for biomarkers approximately 18 months after baseline

18 months

1 visit (in-person)

Long-term Follow-up

Participants are monitored for changes in tau PET uptake values and associations with cognitive and biomarker measures

5 years

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Flortaucipir radiopharmaceutical
• 18F-MK-6240 radiopharmaceutical
• Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694)

Trial Overview The study aims to compare tau PET radiopharmaceuticals Flortaucipir and MK-6240 in measuring tau tangles in the brain related to Alzheimer's. It will help understand how these tracers can be used in clinical settings by integrating their estimates.

How Is the Trial Designed?

Group I: Individuals across the aging and Alzheimer's disease (AD) spectrum Experimental Treatment 3 Interventions

Approximately 620 individuals (40 young healthy, 280 cognitively unimpaired older, 200 mild cognitive impairment, and 100 Alzheimer's disease dementia) will be enrolled in the HEAD study.

18F-Flortaucipir radiopharmaceutical is already approved in United States, European Union for the following indications:

Approved in United States as Tauvid for:

• Estimating the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adults with cognitive impairment who are being evaluated for Alzheimer's disease

Approved in European Union as Tauvid for:

• Diagnosis of Alzheimer's disease

Who Is Running the Clinical Trial?

Tharick Pascoal

Lead Sponsor

Trials

1

Recruited

620+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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]

The study evaluated the effectiveness of different methods for generating parametric images of the PET tau tracer [18F]flortaucipir in 20 participants (10 Alzheimer's disease patients and 10 controls), finding that both Regional Parametric Modeling (RPM) and Spectral Analysis (SA) produced results comparable to traditional non-linear regression methods.

While the Standardized Uptake Value ratio (SUVr) showed good correlation with other methods, it exhibited bias that varied with uptake time and binding levels, indicating the need for further investigation with larger datasets to fully understand its implications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parametric methods for [18F]flortaucipir PET. Golla, SS., Wolters, EE., Timmers, T., et al.[2023]

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]

An automated method for producing the radiotracer [18F]Flortaucipir was developed, achieving high radiochemical yields of 14.8-16.6% in just 55 minutes, which is essential to meet the growing clinical demand for Alzheimer's disease diagnostics.

The final product demonstrated excellent quality, with radiochemical purities exceeding 99.9% and molar activities between 247.9-384.8 GBq/µmol, confirming its safety and efficacy for human use under GMP compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated production of [18F]Flortaucipir for PET imaging of tauopathies. Jiang, H., Jain, MK., Cai, H.[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]

The review highlights that various tau PET tracers, including the FDA-approved 18F-flortaucipir, effectively discriminate between Alzheimer's disease (AD) patients and healthy controls, with effect sizes (Cohen's d) typically ranging from two to three in affected brain regions.

While second-generation tau tracers show improved off-target binding profiles, they do not significantly enhance sensitivity for distinguishing AD from healthy controls, suggesting a potential limit in the affinity of current tracers for tau fibrils.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Sensitivity of Tau Tracers for the Discrimination of Alzheimer's Disease Patients and Healthy Controls by PET. Mohammadi, Z., Alizadeh, H., Marton, J., et al.[2023]

Citations

1. 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]

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

Parametric methods for [18F]flortaucipir PET. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

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

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

Automated production of [18F]Flortaucipir for PET imaging of tauopathies. [2021]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

The Sensitivity of Tau Tracers for the Discrimination of Alzheimer's Disease Patients and Healthy Controls by PET. [2023]