Head-to-Head Harmonization of Tau Tracers in Alzheimer's Disease (HEAD)

Tharick Pascoal

Status and phase: Enrolling; Phase 1

Conditions: Alzheimer Disease

Treatments: Drug: Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694 or 18F-Florbetapir); Drug: 18F-MK-6240 radiopharmaceutical; Drug: 18F-Flortaucipir radiopharmaceutical

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05361382

STUDY22020056

R01AG073267 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this study is to compare/harmonize cross-sectional and longitudinal tau tangle measurements obtained with the tau PET radiopharmaceuticals Flortaucipir and MK-6240 to elucidate the advantages and caveats of their use in clinical trials/practice and provide parameters to integrate their estimates.

Full description

This is a longitudinal, multi-site, non-randomized study in which the participants will undergo Flortaucipir and MK-6240 PET scans at baseline and approximately at 18-month follow-up. At each time point, participants will also have an amyloid-β PET scan, magnetic resonance imaging, detailed cognitive tests, and a blood draw for biomarker quantification. The main objectives of this study are standardizing tau PET tracers' outcomes and comparing their performance.

To accomplish our objectives, the investigators propose the following specific aims:

In Aim 1, investigators will standardize tau PET processing methods, convert the tracers to a common scale, compare associations with amyloid-β, atrophy, and cognition, and compare/harmonize Braak staging assessments between tau tracers using cross-sectional data.

In Aim 2, investigators will ascertain the optimal processing method for longitudinal analysis and compare longitudinal changes in tau accumulation obtained with the tau PET radiopharmaceuticals and their associations with changes in amyloid-β, atrophy, and cognition.

In Exploratory Aim 3, investigators will compare cross-sectional and longitudinal Flortaucipir and MK-6240 estimates with plasma phosphorylated tau concentrations.

This study will produce a benchmark dataset to develop methods for tau PET quantification and harmonization.

Enrollment: 620 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Have an informant who will be able to provide an independent evaluation of functioning.
• Willing and capable of undergoing repeated MR/PET imaging.
• Fluent in a language approved by the coordinating center.
• At screening, must have no cognitive impairment, or meet criteria for single- or multiple-domain amnestic mild cognitive impairment or Alzheimer's disease dementia.

Exclusion criteria

• Inability to provide informed consent by self or by proxy.
• Pregnant or breastfeeding women.
• Have any condition or are taking any medication that could increase the risk to the participant, limit the ability to tolerate or interfere with the results of the tests and procedures (in the opinion of the investigator).

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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620 participants in 1 patient group

Individuals across the aging and Alzheimer's disease (AD) spectrum

Experimental group

Description:

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.

Treatment:

Drug: 18F-Flortaucipir radiopharmaceutical

Drug: 18F-MK-6240 radiopharmaceutical

Drug: Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694 or 18F-Florbetapir)