18F-AV-1451 Autopsy Study

September 3, 2020 updated by: Avid Radiopharmaceuticals

A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology

This study is designed to test the relationship between ante-mortem flortaucipir Positron Emission Tomography (PET) imaging and tau neurofibrillary pathology associated with Alzheimer's disease (AD), as measured at autopsy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

156

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3010
        • University of Melbourne
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Alzheimer's Institute
      • Phoenix, Arizona, United States, 85013
        • St. Joseph's Hospital and Medical Center
    • California
      • Los Gatos, California, United States, 95032
        • Cherlin Research
      • Newport Beach, California, United States, 92658
        • HOAG Memorial Hospital Presbyterian
      • San Diego, California, United States, 92103
        • Pacific Research Network
      • San Diego, California, United States, 92103
        • California Research Foundation
      • San Francisco, California, United States, 94114
        • Ray Dolby Brain Health Center
      • Santa Ana, California, United States, 92705
        • Syrentis Clinical Research
    • Florida
      • Fort Myers, Florida, United States, 33912
        • Neuropsychiatric Research Center of Southwest Florida
      • Hialeah, Florida, United States, 33016
        • Galiz Research
      • Merritt Island, Florida, United States, 32952
        • Merritt Island Medical Research
      • Miami, Florida, United States, 33137
        • Miami Jewish Health Systems
      • Miami, Florida, United States, 33185
        • D De La Vega MD Research Group
      • Orlando, Florida, United States, 32806
        • Bioclinica
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory University Brain Health Center
    • Massachusetts
      • Quincy, Massachusetts, United States, 02169
        • Alzheimer's Disease Center
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Steinberg Diagnostics
    • New York
      • Glens Falls, New York, United States, 12801
        • Adirondack Medical Research Center
      • Syracuse, New York, United States, 13210
        • Clarity Clinical Research, LLC
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest School of Medicine
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Valley Medical Primary Care
      • Cleveland, Ohio, United States, 44119
        • Hospice of the Western Reserve
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • American Clinical Trials, LLC (Site 1216)
      • Oklahoma City, Oklahoma, United States, 73112
        • Oklahoma Behavioral Health
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Houston Methodist Research Institute
      • Kerrville, Texas, United States, 78028
        • Sante Clinical Research
    • Washington
      • Bellevue, Washington, United States, 98004
        • Overlake Internal Medicine Associates, PS
      • Seattle, Washington, United States, 98104
        • University of Washington Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have a projected life expectancy of ≤ 6 months
  • Can tolerate a 20 minute PET scan
  • Give informed consent or have a legally authorized representative to consent for study procedures and brain donation consistent with the legal requirements of the State in which they die

Exclusion Criteria:

  • Aggressively being treated with life sustaining measures
  • Known to have a structural brain lesion that would interfere either with PET imaging or pathological assessment
  • Clinically significant infectious disease
  • Currently receiving any investigational medications except with permission from the study sponsor
  • Participated in an experimental study with an amyloid or tau targeting agent
  • Suspected encephalopathy due to alcoholism or end-stage liver disease
  • Females of childbearing potential
  • History of risk factors for Torsades de Pointes or are currently taking medication known to cause QT prolongation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Flortaucipir PET Scan
Drug: Flortaucipir F18
370 megabecquerel (MBq) IV single-dose
Other Names:
  • 18F-AV-1451
  • [F-18]T807
  • LY3191748
Procedure: PET Scan
positron emission tomography (PET) scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome 1: Diagnostic Performance of Individual Readers (NFT Score)
Time Frame: at autopsy within 9 months of baseline scan
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir PET imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (Braak Stage 0; no NFTs in the brain) to B3 (Braak Stage V/VI; widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.
at autopsy within 9 months of baseline scan
Primary Outcome 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)
Time Frame: at autopsy within 9 months of baseline scan
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to high levels of Alzheimer's disease neuropathologic change (High ADNC) as defined by National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. ADNC categories are None, Low, Intermediate and High, with High indicating the most severe level of AD-related pathology changes in the brain (Hyman et al., Alzheimers Dement. 2012 Jan;8(1):1-13). The hypothesis tested was that, of the 5 independent imaging physicians, at least 3 will have the lower bounds of 2-sided 95% CIs ≥50%, for both sensitivity and specificity.
at autopsy within 9 months of baseline scan

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Flortaucipir Diagnostic Performance (NFT Score)
Time Frame: at autopsy within 9 months of baseline scan
Sensitivity and specificity of majority interpretation of AD pattern tau PET scan corresponding to NFT Score of B3. The 95% confidence intervals (CI) provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity.
at autopsy within 9 months of baseline scan
Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis)
Time Frame: at autopsy within 9 months of baseline scan
Sensitivity and specificity of majority interpretation of of AD pattern tau PET scan corresponding to NIA-AA autopsy diagnosis. The 95% CIs provided for specificity and sensitivity were based on the Wilson score method. The hypothesis tested was that majority read results had the lower bound of the 2-sided 95% CI greater than or equal to 55% for both sensitivity and specificity.
at autopsy within 9 months of baseline scan
Inter-Reader Agreement
Time Frame: baseline scan
Fleiss' Kappa statistics were used to assess inter-reader agreement for the diagnostic decisions associated with primary outcome 1. Fleiss' kappa is a statistical measure for assessing the reliability of agreement between a fixed number of raters when assigning categorical ratings to a number of items or classifying items. Fleiss' kappa can range from 0 to 1 with 1 indicating perfect agreement between the readers. Results are reported as overall agreement, calculated as proportion of scans where reader pairs agreed, divided by the total number of scans read by each reader pair.
baseline scan

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Performance of Individual Readers (NFT Score B2-B3 as Truth Positive)
Time Frame: at autopsy within 9 months of baseline scan
Sensitivity and specificity of 5 independent readers' interpretations of ante-mortem flortaucipir PET imaging for detection of a pattern of flortaucipir neocortical uptake that corresponds to neurofibrillary tangles (NFT) Score of B3 (Hyman et al., 2012; Montine et al., 2012). NFT B scores range from B0 (no NFTs in the brain) to B3 (widespread NFTs in the brain). Sensitivity and specificity are percentages that can range from 0 to 100%. For this analysis, B scores of B2-B3 were considered truth positive, and B scores of B0-B1 were considered truth negative.
at autopsy within 9 months of baseline scan

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Avid Radiopharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (ACTUAL)

June 13, 2018

Study Completion (ACTUAL)

July 15, 2018

Study Registration Dates

First Submitted

August 3, 2015

First Submitted That Met QC Criteria

August 3, 2015

First Posted (ESTIMATE)

August 5, 2015

Study Record Updates

Last Update Posted (ACTUAL)

September 7, 2020

Last Update Submitted That Met QC Criteria

September 3, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18F-AV-1451-A16

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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