Tau Tracer Comparison for Alzheimer's Disease

(HEAD Trial)

Not currently recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two imaging substances, 18F-Flortaucipir radiopharmaceutical and 18F-MK-6240 radiopharmaceutical, to assess their effectiveness in detecting Alzheimer's disease. The researchers aim to understand the advantages and disadvantages of these substances in brain scans for tracking tau tangles, which are linked to Alzheimer's. Individuals with no cognitive issues, mild memory problems, or Alzheimer's who can undergo brain scans may be suitable for this trial. Participants must also have a study partner to assist with evaluations and speak a language approved by the study center. 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.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have safely used 18F-Flortaucipir in adults for brain imaging to help diagnose Alzheimer's disease. The FDA has approved it for this purpose, indicating general safety. However, some side effects have been reported, and researchers continue to study its overall safety and effectiveness.

Research has shown that 18F-MK-6240 is a promising tool for imaging brain changes related to Alzheimer's and other conditions. As it remains in early testing, detailed safety information is not yet available, but researchers are carefully studying potential risks and benefits.

Both treatments involve a PET scan, which is usually considered low-risk. Participants should be aware of common imaging side effects and discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they use two novel radiopharmaceuticals, 18F-Flortaucipir and 18F-MK-6240, which are designed to visualize tau protein deposits in the brain, a hallmark of Alzheimer's disease. Unlike standard treatments that focus on managing symptoms or targeting amyloid plaques, these radiopharmaceuticals provide a clearer picture of tau pathology, potentially leading to earlier and more precise diagnosis. This innovative approach could revolutionize how we understand and track the progression of Alzheimer's, offering insights that could inform the development of more effective therapies in the future.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research has shown that the 18F-Flortaucipir radiopharmaceutical, which participants in this trial may receive, effectively images tau proteins in the brain linked to Alzheimer's disease. Studies have demonstrated that it accurately highlights areas of tau buildup, matching patterns seen in Alzheimer's patients. This clarity helps doctors better understand how Alzheimer's affects the brain.

Similarly, 18F-MK-6240, another tracer under study in this trial, also targets tau proteins. Early findings suggest it provides clear images of tau deposits with minimal interference from other brain activities. Both radiopharmaceuticals are promising tools for better understanding and diagnosing Alzheimer's disease. ^{4 6 7 8 9}

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.

I am between 50 and 90 years old.

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

All individuals enrolled into the HEAD study will undergo tau PET, amyloid-β PET, magnetic resonance imaging (MRI), detailed clinical and cognitive assessment, and a blood draw.

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]

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 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]

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]

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]

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. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251403

Integrating 18F-flortaucipir (TAUVID) PET/CT/MRI into ... NFT deposition patterns correlate more closely with cognitive decline and AD severity compared to amyloid plaque presence and decreased brain ...

3. nature.com nature.com/articles/s41598-023-35389-w

Deep learning application for the classification of ... - Nature This study aimed to evaluate the utility of 18 F-flortaucipir-PET images and multimodal data integration in the differentiation of CU from MCI or AD through DL.

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

Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau ... The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04080544?intr=FLORTAUCIPIR%20(18F)&aggFilters=studyType:int&viewType=Table&rank=2

Cognitive Decline and Alzheimer's Disease in the Dallas ... The objective of the current study is to test 125 DLBS participants with [18F]AV-1451 (Flortaucipir F 18) at the University of Texas Southwestern Medical Center ...

6. ema.europa.eu ema.europa.eu/en/medicines/human/EPAR/tauvid

Tauvid | European Medicines Agency (EMA) Flortaucipir (18F) is a radiopharmaceutical indicated for positron emission tomography (PET) imaging of the brain to assess the neocortical ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/flortaucipir-f-18-intravenous-route/description/drg-20489619

Flortaucipir f 18 (intravenous route) - Side effects & uses Flortaucipir F 18 injection is used to help diagnose Alzheimer's disease in adults. ... Safety and efficacy have not been established.

8. pi.lilly.com pi.lilly.com/us/tauvid-uspi.pdf

tauvid-uspi.pdf The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. Preliminary non- clinical and clinical investigations ...

9. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b483abad-5230-462a-adfb-1a65160f01d0

TAUVID- flortaucipir f-18 injection, solution - DailyMed 5 WARNINGS AND PRECAUTIONS. 5.1 Risk of Misdiagnosis in Patients Evaluated for Alzheimer's disease - TAUVID does not target β-amyloid, ...