Clinical trial NCT05361382: Head-to-Head Harmonization of Tau Tracers in Alzheimer's Disease
Official title: Longitudinal Multicenter Head-to-Head Harmonization of Tau PET Tracers
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: Tau PET
Neurofibrillary tangles
Alzheimer's disease
Tauopathies
Biomarkers
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2022-05-04
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Cross-sectional tau PET uptake values
timeFrame: 2 years from enrollment
measure: Longitudinal change in tau PET uptake values over 18 months
timeFrame: 5 years from enrollment
Secondary outcomes:
measure: Associations of tau PET uptake values with amyloid-β PET uptake values
timeFrame: 5 years from enrollment
measure: Associations of tau PET uptake values with measures of cognition
timeFrame: 5 years from enrollment
measure: Associations of tau PET uptake values blood biomarkers
timeFrame: 5 years from enrollment
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Lawrence Berkeley National Laboratory
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Montréal
country: Canada
facility: McGill University
state: Quebec
city: Barcelona
country: Spain
facility: Sant Pau Biomedical Research Institute
Study officials:
affiliation: University of Pittsburgh
name: Tharick Pascoal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: