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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05361382
Recruitment Status : Not yet recruiting
First Posted : May 4, 2022
Last Update Posted : May 4, 2022
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Tharick Pascoal, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: 18F-Flortaucipir radiopharmaceutical Drug: 18F-MK-6240 radiopharmaceutical Drug: Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 620 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Longitudinal Multicenter Head-to-Head Harmonization of Tau PET Tracers
Estimated Study Start Date : June 2022
Estimated Primary Completion Date : May 31, 2027
Estimated Study Completion Date : May 31, 2027

Resource links provided by the National Library of Medicine


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 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)

The clinical sites will use either PiB, Florbetaben, 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.





Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.



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Ages Eligible for Study:   20 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05361382


Contacts
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Contact: Tharick Pascoal, MD PhD 412-246-5147 pascoalt@upmc.edu
Contact: Firoza Z Lussier, MSc 412-586-9012 lussierfz@upmc.edu

Locations
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United States, California
Lawrence Berkeley National Laboratory
Berkeley, California, United States, 94720
Contact: Suzanne Baker, PhD       slbaker@lbl.gov   
University of California San Francisco
San Francisco, California, United States, 94143
Contact: David Soleimani-Meigooni, MD       david.soleimani-meigooni@ucsf.edu   
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Contact: Val Lowe, MD       vlowe@mayo.edu   
United States, Missouri
Washington University in St. Louis
Saint Louis, Missouri, United States, 63130
Contact: Brian A Gordon, PhD       bagordon@wustl.edu   
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15260
Contact: Tharick Pascoal, MD PhD       pascoalt@upmc.edu   
Contact: Firoza Z Lussier, MSc    412-586-9012    lussierfz@upmc.edu   
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02912
Contact: Hwamee Oh, PhD       hwamee_oh@brown.edu   
United States, Texas
Houston Methodist Neurological Institute
Houston, Texas, United States, 77030
Contact: Maria B Pascual, PhD       bpascual@houstonmethodist.org   
Canada, Quebec
McGill University Research Centre for Studies in Aging
Montréal, Quebec, Canada, H4H1V3
Contact: Pedro Rosa-Neto, MD, PhD       pedro.rosa@mcgill.ca   
Sponsors and Collaborators
Tharick Pascoal
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Tharick Pascoal, MD PhD University of Pittsburgh
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Responsible Party: Tharick Pascoal, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT05361382    
Other Study ID Numbers: STUDY22020056
R01AG073267 ( U.S. NIH Grant/Contract )
First Posted: May 4, 2022    Key Record Dates
Last Update Posted: May 4, 2022
Last Verified: April 2022
Individual Participant Data (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/

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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
Keywords provided by Tharick Pascoal, University of Pittsburgh:
Tau PET
Neurofibrillary tangles
Alzheimer's disease
Tauopathies
Biomarkers
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action