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18F-AV-1451 Autopsy Study

Phase 3
Completed
Conditions
Alzheimer's Disease
Interventions
Procedure: PET Scan
Registration Number
NCT02516046
Lead Sponsor
Avid Radiopharmaceuticals
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
156
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Flortaucipir PET ScanPET Scan-
Flortaucipir PET ScanFlortaucipir F18-
Primary Outcome Measures
NameTimeMethod
Primary Outcome 1: Diagnostic Performance of Individual Readers (NFT Score)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.

Primary Outcome 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)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
NameTimeMethod
Flortaucipir Diagnostic Performance (NFT Score)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.

Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis)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.

Inter-Reader Agreementbaseline 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.

Trial Locations

Locations (31)

Banner Alzheimer's Institute

🇺🇸

Phoenix, Arizona, United States

St. Joseph's Hospital and Medical Center

🇺🇸

Phoenix, Arizona, United States

Cherlin Research

🇺🇸

Los Gatos, California, United States

Hoag Memorial Hospital Presbyterian

🇺🇸

Newport Beach, California, United States

California Research Foundation

🇺🇸

San Diego, California, United States

Pacific Research Network

🇺🇸

San Diego, California, United States

Ray Dolby Brain Health Center

🇺🇸

San Francisco, California, United States

Syrentis Clinical Research

🇺🇸

Santa Ana, California, United States

Neuropsychiatric Research Center of Southwest Florida

🇺🇸

Fort Myers, Florida, United States

Galiz Research

🇺🇸

Hialeah, Florida, United States

Scroll for more (21 remaining)
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States

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