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

Study Overview
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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.

Official Title
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Longitudinal Multicenter Head-to-Head Harmonization of Tau PET Tracers

Conditions
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Alzheimer Disease

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individuals across the aging and Alzheimer's disease (AD) spectrum<br>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. | Drug: 18F-Flortaucipir radiopharmaceutical<br>* 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.<br>* Other names: 18F-AV-1451, 18F-T807, Tauvid;Drug: 18F-MK-6240 radiopharmaceutical<br>* 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.<br>Drug: Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694 or 18F-Florbetapir)<br>* The clinical sites will use either PiB, Florbetaben, Florbetapir, 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 10 millicuries of the Florbetapir radiopharmaceutical.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cross-sectional tau PET uptake values | Compare/harmonize cross-sectional tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240. | 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. | 5 years from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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. | 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. | 5 years from enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tau PET, Neurofibrillary tangles, Alzheimer's disease, Tauopathies, Biomarkers