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18F-AV-1451 Autopsy Study

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02516046
Recruitment Status : Completed
First Posted : August 5, 2015
Results First Posted : September 7, 2020
Last Update Posted : September 7, 2020
Sponsor:
Information provided by (Responsible Party):
Avid Radiopharmaceuticals

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Flortaucipir F18 Procedure: PET Scan Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 156 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: A Clinico-Pathological Study of the Correspondence Between 18F-AV-1451 PET Imaging and Post-Mortem Assessment of Tau Pathology
Study Start Date : September 2015
Actual Primary Completion Date : June 13, 2018
Actual Study Completion Date : July 15, 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Flortaucipir PET Scan Drug: Flortaucipir F18
370 megabecquerel (MBq) IV single-dose
Other Names:
  • [F-18]T807
  • 18F-AV-1451
  • LY3191748

Procedure: PET Scan
positron emission tomography (PET) scan


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Other Outcome Measures:
  1. 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.


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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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): NCT02516046


Locations
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Sponsors and Collaborators
Avid Radiopharmaceuticals
Investigators
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Study Chair: Chief Medical Officer Avid Radiopharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Avid Radiopharmaceuticals:
Study Protocol  [PDF] December 18, 2017
Statistical Analysis Plan  [PDF] August 15, 2018

More Information
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Publications of Results:

Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Avid Radiopharmaceuticals
ClinicalTrials.gov Identifier: NCT02516046    
Other Study ID Numbers: 18F-AV-1451-A16
First Posted: August 5, 2015    Key Record Dates
Results First Posted: September 7, 2020
Last Update Posted: September 7, 2020
Last Verified: September 2020
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