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

• ClinicalTrials.gov Identifier: NCT05361382
• Recruitment Status: Recruiting
• First Posted: May 4, 2022
• Last Update Posted: November 7, 2023
• Sponsor: Tharick Pascoal
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Tharick Pascoal, University of Pittsburgh

Tracking Information

• First Submitted Date: April 29, 2022
• First Posted Date: May 4, 2022
• Last Update Posted Date: November 7, 2023
• Actual Study Start Date: November 23, 2021
• Estimated Primary Completion Date: May 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 29, 2022)

• Cross-sectional tau PET uptake values [ Time Frame: 2 years from enrollment ]
  Compare/harmonize cross-sectional tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240.
• Longitudinal change in tau PET uptake values over 18 months [ Time Frame: 5 years from enrollment ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 29, 2022)

• Associations of tau PET uptake values with amyloid-β PET uptake values [ Time Frame: 5 years from enrollment ]
  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).
• Associations of tau PET uptake values with measures of cognition [ Time Frame: 5 years from enrollment ]
  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.
• Associations of tau PET uptake values blood biomarkers [ Time Frame: 5 years from enrollment ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Head-to-Head Harmonization of Tau Tracers in Alzheimer's Disease
• Official Title: Longitudinal Multicenter Head-to-Head Harmonization of Tau PET Tracers
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Alzheimer Disease

Intervention

• 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 Name: 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.

Study Arms

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.

Interventions:

• 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)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2022): 620
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2027
• Estimated Primary Completion Date: May 31, 2027 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Tharick Pascoal, MD PhD; 412-586-9012; pascoal-research@upmc.edu

• Listed Location Countries: Canada, Spain, United States

Administrative Information

• NCT Number: NCT05361382
• Other Study ID Numbers: STUDY22020056; R01AG073267 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Time Frame: Data from baseline and follow-up assessments will be available for sharing after the completion of the respective study visits.
• 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.
• URL: http://www.loni.usc.edu/

• Current Responsible Party: Tharick Pascoal, University of Pittsburgh
• Original Responsible Party: Same as current
• Current Study Sponsor: Tharick Pascoal
• Original Study Sponsor: Same as current
• Collaborators: National Institute on Aging (NIA)

Investigators

• Principal Investigator: Tharick Pascoal, MD PhD; University of Pittsburgh

• PRS Account: University of Pittsburgh
• Verification Date: November 2023