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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / 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)

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.

• Study Type: Interventional
• Enrollment (Estimated): 620
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tharick Pascoal, MD PhD; Phone Number: 412-586-9012; Email: pascoal-research@upmc.edu

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4H1V3
      • Recruiting
      • McGill University Research Centre for Studies in Aging
      • Contact: Pedro Rosa-Neto, MD, PhD
• Spain
  • Barcelona, Spain, 08025
    • Not yet recruiting
    • Sant Pau Biomedical Research Institute
    • Contact: Juan Fortea, MD, PhD
• United States
  • California
    • Berkeley, California, United States, 94720
      • Recruiting
      • Lawrence Berkeley National Laboratory
      • Contact: Suzanne Baker, PhD
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco
      • Contact: David Soleimani-Meigooni, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Val Lowe, MD
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Recruiting
      • Washington University in St. Louis
      • Contact: Brian A Gordon, PhD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Recruiting
      • University of Pittsburgh
      • Contact: Tharick Pascoal, MD PhD
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Recruiting
      • Brown University
      • Contact: Hwamee Oh, PhD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Neurological Institute
      • Contact: Maria B Pascual, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Individuals across the aging and Alzheimer's disease (AD) spectrum; 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; 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.; Other Names: 18F-AV-1451, 18F-T807, Tauvid; 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.; Drug: Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694 or 18F-Florbetapir); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tharick Pascoal
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Tharick Pascoal, MD PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Biomarkers; Tauopathies; Tau PET; Neurofibrillary tangles
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals
• Other Study ID Numbers: STUDY22020056; R01AG073267 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this research will be shared with other researchers pursuant to the 02/26/2003 "NIH Final Statement on Sharing Research Data". To protect participants' rights and confidentiality, identifiers will be removed from the data before they are shared. The board of PIs has primary oversight of the HEAD study resource sharing plan and will review all issues related to internal and external requests for HEAD data. Raw PET and MR data will be uploaded by clinical sites after acquisitions, whereas processed PET and MR data will be uploaded after completion of the baseline visit and after completion of the 18-month follow-up visit. Demographics, results from cognitive tests, Aβ status, tau Braak staging, and plasma assay results will also be available through the LONI platform.
• IPD Sharing Time Frame: Data from baseline and follow-up assessments will be available for sharing after the completion of the respective study visits.
• IPD Sharing Access Criteria: Researchers will be able to download data upon request to the PIs. Data sharing requests will be overseen by the study and site PIs.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No