Autopsy Follow-up of Subjects Previously Imaged With Florbetapir F 18 (18F-AV-45) PET in Trial 18F-AV-45-A07

This study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid plaque density as measured by histopathological assessment. The study will address the following specific aims:

1. To expand the number of subjects included in the A07 (NCT00857415) trial correlation analysis (measuring the correlation between the global visual rating of brain amyloid plaque density on an independent blinded read of the florbetapir F 18 PET scan and the cortical amyloid plaque density at autopsy as assessed by histopathology for subjects in the autopsy cohort).
2. To determine the sensitivity and specificity of an independent blinded visual read assessment of the florbetapir F 18 PET scan (Aβ+ or Aβ-) versus the final blinded neuropathological assessment made at autopsy.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: florbetapir F 18

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoeniz, Arizona, United States, 85006
      • Research Site
    • Sun City, Arizona, United States, 85351
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Research Site
  • California
    • Irvine, California, United States, 92697
      • Research Site
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Research Site
    • Miami, Florida, United States, 33137
      • Research Site
    • Miami Beach, Florida, United States, 33140
      • Research Site
    • Miami Springs, Florida, United States, 33166
      • Research Site
    • Orlando, Florida, United States, 32835
      • Research Site
    • Sarasota, Florida, United States, 34231
      • Research Site
    • St. Petersburg, Florida, United States, 33709
      • Research Site
    • West Palm Beach, Florida, United States, 33407
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21221
      • Research Site
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Research Site
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Research Site
  • New York
    • Albany, New York, United States, 12208
      • Research Site
    • New Hyde Park, New York, United States, 11040
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Research Site
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Research Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37614
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects are enrolled in this study if they:

• Met entrance criteria and were enrolled and imaged in trial 18F-AV-45-A07 (NCT00857415)
• Gave informed consent for the 18F-AV-45-A07 (NCT00857415) study procedures and brain donation consistent with the legal requirements of the State in which they are enrolled and the State in which they die
• Consent to participate in the 18F-AV-45-A16 (NCT01447719) extension protocol, if required by the IRB
• Reconfirm their consent to a research brain autopsy, if required by the IRB.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity Analysis in All Autopsy Population	Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD (Consortium to Establish a Registry for AD) criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).	at autopsy within 24 months of florbetapir PET scan
Specificity Analysis in All Autopsy Population	Specificity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).	at autopsy within 24 months of florbetapir PET scan
Correlation of Florbetapir-PET Image and Amyloid Plaque Density	Spearman's rank order correlation of the median visual read of the florbetapir-PET image and the amyloid plaque density assessed post-mortem by quantitative immunohistochemistry (IHC) averaged across 6 brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate). Spearman's rank order correlation ranges from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.	at autopsy within 24 months of florbetapir PET scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity Analysis in Subjects With Autopsy Within 1 Year of Scan	Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).	at autopsy within 12 months of florbetapir PET scan
Specificity Analysis in Subjects With Autopsy Within 1 Year of Scan	Specificity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative).	at autopsy within 12 months of florbetapir PET scan

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Sensitivity and Specificity vs. CERAD Diagnosis	Median sensitivity and specificity for 5 independent readers to detect moderate to frequent amyloid plaques (per CERAD criteria).	at autopsy within 24 months of florbetapir PET scan
Individual Reader Results (All Scans With Autopsy)	Reader results (number of false negatives and number of false positives) for blinded independent readers. There were a total of 39 positive and 20 negative scans based on histopathology at autopsy.	at autopsy within 24 months of florbetapir PET scan
Individual Reader Results (Autopsy Within 1 Year of Scan)	Reader results (number of false negatives and number of false positives) for blinded independent readers. There were a total of 28 positive and 18 negative scans based on histopathology at autopsy.	at autopsy within 12 months of florbetapir PET scan

Collaborators and Investigators

• Sponsor: Avid Radiopharmaceuticals

Publications and helpful links

General Publications

• Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM; AV-45-A16 Study Group. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol. 2012 Aug;11(8):669-78. doi: 10.1016/S1474-4422(12)70142-4. Epub 2012 Jun 28. Erratum In: Lancet Neurol. 2012 Aug;11(8):658.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 20, 2011
• First Submitted That Met QC Criteria: October 5, 2011
• First Posted (Estimate): October 6, 2011

Study Record Updates

• Last Update Posted (Estimate): May 22, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 18F-AV-45-A16