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

Primary Purpose

Alzheimer Disease

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
18F-Flortaucipir radiopharmaceutical
18F-MK-6240 radiopharmaceutical
Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694)
Sponsored by
Tharick Pascoal
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Alzheimer Disease focused on measuring Tau PET, Neurofibrillary tangles, Alzheimer's disease, Tauopathies, Biomarkers

Eligibility Criteria

20 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

  • Lawrence Berkeley National LaboratoryRecruiting
  • University of California San Francisco
  • Mayo Clinic
  • Washington University in St. LouisRecruiting
  • University of PittsburghRecruiting
  • Brown University
  • Houston Methodist Neurological InstituteRecruiting
  • McGill University Research Centre for Studies in AgingRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Individuals across the aging and Alzheimer's disease (AD) spectrum

Arm Description

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.

Outcomes

Primary Outcome Measures

Cross-sectional tau PET uptake values
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
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

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).
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.
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.

Full Information

First Posted
April 29, 2022
Last Updated
May 2, 2023
Sponsor
Tharick Pascoal
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT05361382
Brief Title
Head-to-Head Harmonization of Tau Tracers in Alzheimer's Disease
Acronym
HEAD
Official Title
Longitudinal Multicenter Head-to-Head Harmonization of Tau PET Tracers
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 23, 2021 (Actual)
Primary Completion Date
May 31, 2027 (Anticipated)
Study Completion Date
May 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Tharick Pascoal
Collaborators
National Institute on Aging (NIA)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Tau PET, Neurofibrillary tangles, Alzheimer's disease, Tauopathies, Biomarkers

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
620 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Individuals across the aging and Alzheimer's disease (AD) spectrum
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
18F-Flortaucipir radiopharmaceutical
Other Intervention Name(s)
18F-AV-1451, 18F-T807, Tauvid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
18F-MK-6240 radiopharmaceutical
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Amyloid-β radiopharmaceutical (11C-PiB or 18F-Florbetaben or 18F-NAV-4694)
Intervention Description
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 Measure Information:
Title
Cross-sectional tau PET uptake values
Description
Compare/harmonize cross-sectional tau deposition measurements (standardized uptake value ratio (SUVR)) obtained with Flortaupicir and MK-6240.
Time Frame
2 years from enrollment
Title
Longitudinal change in tau PET uptake values over 18 months
Description
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.
Time Frame
5 years from enrollment
Secondary Outcome Measure Information:
Title
Associations of tau PET uptake values with amyloid-β PET uptake values
Description
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).
Time Frame
5 years from enrollment
Title
Associations of tau PET uptake values with measures of cognition
Description
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.
Time Frame
5 years from enrollment
Title
Associations of tau PET uptake values blood biomarkers
Description
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.
Time Frame
5 years from enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tharick Pascoal, MD PhD
Phone
412-586-9012
Email
pascoal-research@upmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tharick Pascoal, MD PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lawrence Berkeley National Laboratory
City
Berkeley
State/Province
California
ZIP/Postal Code
94720
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suzanne Baker, PhD
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Soleimani-Meigooni, MD
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Val Lowe, MD
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian A Gordon, PhD
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15260
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tharick Pascoal, MD PhD
Facility Name
Brown University
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02912
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hwamee Oh, PhD
Facility Name
Houston Methodist Neurological Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria B Pascual, PhD
Facility Name
McGill University Research Centre for Studies in Aging
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4H1V3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pedro Rosa-Neto, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
http://www.loni.usc.edu/

Learn more about this trial

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

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