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

Phase 1Active Not RecruitingNCT05361382

Tharick Pascoal822 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

822

Conditions

Alzheimer Disease

Interventions

18F-Flortaucipir radiopharmaceuticalDRUG

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 radiopharmaceuticalDRUG

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)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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (9)

Lawrence Berkeley National Laboratory

Berkeley, California, United States

University of California San Francisco

San Francisco, California, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University in St. Louis

Outcomes

Primary Outcomes

Cross-sectional tau PET uptake values

Compare/harmonize cross-sectional tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240.

Time frame: 2 years from enrollment

Longitudinal change in tau PET uptake values over 18 months

Compare/harmonize change in tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240 between baseline and 18-month follow-up assessments.

Time frame: 5 years from enrollment

Secondary Outcomes

Associations of tau PET uptake values with amyloid-β PET uptake values

Compare the effect size of the associations of tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240 with amyloid-β deposition measurements (SUVR).

Time frame: 5 years from enrollment

Associations of tau PET uptake values with measures of cognition

Compare the effect size of the associations of tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240 with cognitive measures assessed from neuropsychological evaluation.

Time frame: 5 years from enrollment

Associations of tau PET uptake values blood biomarkers

Compare the effect size of the associations of tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240 with blood-based biomarkers of tau.

Time frame: 5 years from enrollment

Data from ClinicalTrials.gov

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