18F-AV-1451 Autopsy Study

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02516046
• Other study ID #: 18F-AV-1451-A16
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: July 15, 2018

Study information

• Verified date: September 2020
• Source: Avid Radiopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: July 15, 2018
• Est. primary completion date: June 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Flortaucipir F18
370 megabecquerel (MBq) IV single-dose

Procedure:
• PET Scan
positron emission tomography (PET) scan

Locations

Country	Name	City	State
Australia	University of Melbourne	Parkville	Victoria
United States	Emory University Brain Health Center	Atlanta	Georgia
United States	Overlake Internal Medicine Associates, PS	Bellevue	Washington
United States	Valley Medical Primary Care	Centerville	Ohio
United States	Hospice of the Western Reserve	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida
United States	Adirondack Medical Research Center	Glens Falls	New York
United States	Steinberg Diagnostics	Henderson	Nevada
United States	Galiz Research	Hialeah	Florida
United States	Houston Methodist Research Institute	Houston	Texas
United States	Sante Clinical Research	Kerrville	Texas
United States	Cherlin Research	Los Gatos	California
United States	Merritt Island Medical Research	Merritt Island	Florida
United States	D de la Vega MD Research Group	Miami	Florida
United States	Miami Jewish Health Systems	Miami	Florida
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	American Clinical Trials, LLC (Site 1216)	Oklahoma City	Oklahoma
United States	Oklahoma Behavioral Health	Oklahoma City	Oklahoma
United States	Bioclinica	Orlando	Florida
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Alzheimer's Disease Center	Quincy	Massachusetts
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	University of Washington Medicine	Seattle	Washington
United States	Clarity Clinical Research, LLC	Syracuse	New York
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Avid Radiopharmaceuticals

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (3)

Fleisher AS, Pontecorvo MJ, Devous MD Sr, Lu M, Arora AK, Truocchio SP, Aldea P, Flitter M, Locascio T, Devine M, Siderowf A, Beach TG, Montine TJ, Serrano GE, Curtis C, Perrin A, Salloway S, Daniel M, Wellman C, Joshi AD, Irwin DJ, Lowe VJ, Seeley WW, Ik — View Citation

Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012 Jan;8(1):1-13. doi: 10.1016/j.jalz.2011.10.007. — View Citation

Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT; National Institute on Aging; Alzheimer's Association. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2012 Jan;123(1):1-11. doi: 10.1007/s00401-011-0910-3. Epub 2011 Nov 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Diagnostic Performance of Individual Readers (NFT Score B2-B3 as Truth Positive)	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
Primary	Primary Outcome 1: Diagnostic Performance of Individual Readers (NFT Score)	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	Primary Outcome 2: Diagnostic Performance of Individual Readers (NIA-AA Autopsy Diagnosis)	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	Flortaucipir Diagnostic Performance (NFT Score)	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
Secondary	Flortaucipir Diagnostic Performance (NIA-AA Autopsy Diagnosis)	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
Secondary	Inter-Reader Agreement	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