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

NCT ID: NCT05361382

Last Updated: 2025-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

822 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-02

Study Completion Date

2027-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Alzheimer Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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

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.

Group Type EXPERIMENTAL

18F-Flortaucipir radiopharmaceutical

Intervention Type DRUG

Flortaucipir is a PET radiopharmaceutical that binds to tau neurofibrillary tangles. Participants will receive a bolus intravenous injection of approximately 10 millicuries of the radiopharmaceutical.

18F-MK-6240 radiopharmaceutical

Intervention Type DRUG

MK-6240 is a PET radiopharmaceutical that binds to tau neurofibrillary tangles. Participants will receive a bolus intravenous injection of approximately 5 millicuries of the radiopharmaceutical.

Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694 or 18F-Flutemetamol)

Intervention Type DRUG

The clinical sites will use either PiB, Florbetaben, Flutemetamol, or NAV-4694 as the amyloid-β PET radiopharmaceutical. The amyloid-β PET radiopharmaceutical binds to amyloid-β plaques.

Participants will receive a bolus intravenous injection of approximately 15 millicuries of the PiB radiopharmaceutical.

Participants will receive a bolus intravenous injection of approximately 8 millicuries of the Florbetaben or NAV-4694 radiopharmaceutical.

Participants will receive a bolus intravenous injection of approximately 5 millicuries of the Flutemetamol radiopharmaceutical.

Interventions

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18F-Flortaucipir radiopharmaceutical

Flortaucipir is a PET radiopharmaceutical that binds to tau neurofibrillary tangles. Participants will receive a bolus intravenous injection of approximately 10 millicuries of the radiopharmaceutical.

Intervention Type DRUG

18F-MK-6240 radiopharmaceutical

MK-6240 is a PET radiopharmaceutical that binds to tau neurofibrillary tangles. Participants will receive a bolus intravenous injection of approximately 5 millicuries of the radiopharmaceutical.

Intervention Type DRUG

Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694 or 18F-Flutemetamol)

The clinical sites will use either PiB, Florbetaben, Flutemetamol, or NAV-4694 as the amyloid-β PET radiopharmaceutical. The amyloid-β PET radiopharmaceutical binds to amyloid-β plaques.

Participants will receive a bolus intravenous injection of approximately 15 millicuries of the PiB radiopharmaceutical.

Participants will receive a bolus intravenous injection of approximately 8 millicuries of the Florbetaben or NAV-4694 radiopharmaceutical.

Participants will receive a bolus intravenous injection of approximately 5 millicuries of the Flutemetamol radiopharmaceutical.

Intervention Type DRUG

Other Intervention Names

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18F-AV-1451, 18F-T807, Tauvid

Eligibility Criteria

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Inclusion Criteria

* Have a study partner 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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Tharick Pascoal

OTHER

Sponsor Role lead

Responsible Party

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Tharick Pascoal

Associate Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Tharick Pascoal, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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Lawrence Berkeley National Laboratory

Berkeley, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University in St. Louis

St Louis, Missouri, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Brown University

Providence, Rhode Island, United States

Site Status

Houston Methodist Neurological Institute

Houston, Texas, United States

Site Status

McGill University

Montreal, Quebec, Canada

Site Status

Sant Pau Biomedical Research Institute

Barcelona, Spain, Spain

Site Status

Countries

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United States Canada Spain

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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R01AG073267

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY22020056

Identifier Type: -

Identifier Source: org_study_id

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