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

Alzheimer Disease Clinical Trial

— HEAD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05361382
• Other study ID #: STUDY22020056
• Secondary ID: R01AG073267
• Status: Recruiting
• Phase: Phase 1
• Start date: November 23, 2021
• Est. completion date: May 31, 2027

Study information

• Verified date: November 2023
• Source: University of Pittsburgh
• Contact: Tharick Pascoal, MD PhD
• Phone: 412-586-9012
• Email: pascoal-research[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 620
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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).

Related Conditions & MeSH terms

• 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.
• 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.
• Amyloid-ß 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-ß PET radiopharmaceutical. The amyloid-ß PET radiopharmaceutical binds to amyloid-ß 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.

Locations

Country	Name	City	State
Canada	McGill University Research Centre for Studies in Aging	Montréal	Quebec
Spain	Sant Pau Biomedical Research Institute	Barcelona
United States	Lawrence Berkeley National Laboratory	Berkeley	California
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Brown University	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Tharick Pascoal	National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Associations of tau PET uptake values with amyloid-ß 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-ß deposition measurements (SUVR).	5 years from enrollment
Secondary	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
Secondary	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