Alzheimer's Disease
Conditions
Brief summary
The study is designed to examine the relationship between imaging results detected on a 18F-AV-1451 PET scan and pathology found at autopsy within six months of imaging.
Interventions
DRUGFlortaucipir F18
Subjects will receive a single IV bolus injection of 370 megabecquerel (MBq) (10 millicurie \[mCi\]) of flortaucipir.
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 89 Years
Healthy volunteers
No
Inclusion criteria
* Projected life expectancy ≤ 6 months
Exclusion criteria
* Primary brain tumor, known metastases to the brain, central nervous system lymphoma * Major, focal structural brain lesion * Aggressively being treated with life sustaining measures * Clinically significant infectious disease * History of risk factors for Torsades de Pointes or are currently taking medication known to cause QT prolongation * Have received or participated in a trial with investigational medications in the past 30 days * Females of childbearing potential who are pregnant or not using adequate contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relationship of Flortaucipir Scan and Pathology - Whole Cortical Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of whole cortical global quantitation of the PET scan from 82 FreeSurfer-defined regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
| Relationship of Flortaucipir Scan and Pathology - Frontal Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of frontal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
| Relationship of Flortaucipir Scan and Pathology - Parietal Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of parietal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
| Relationship of Flortaucipir Scan and Pathology - Cingulate Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of cingulate composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
| Relationship of Flortaucipir Scan and Pathology - Temporal Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of temporal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
| Relationship of Flortaucipir Scan and Pathology - Occipital Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of occipital composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
| Relationship of Flortaucipir Scan and Pathology - Limbic Composite Region | autopsy within 6 months of scan | Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of limbic composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. |
Countries
United States
Participant flow
Recruitment details
Enrollment was opened in June 2015 and closed in May 2018. First patient enrolled in November 2016 and last enrolled patient completed the study procedures in June 2017. Study enrolled end-of-life subjects (life expectancy less than 6 months) at medical centers in the US who consented to a flortaucipir PET scan and to brain donation at autopsy.
Pre-assignment details
To be considered eligible for the primary analysis, death had to occur within 6 months of flortaucipir scan and valid autopsy was required.
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled Cohort End-of-life subjects (life expectancy \< 6 months) consenting to brain donation at autopsy. Subjects received a single IV bolus injection of 370 MBq (10 mCi) of flortaucipir. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | subject survived greater than 6 months following dosing | 1 |
Baseline characteristics
| Characteristic | All Enrolled Cohort |
|---|---|
| Age, Continuous | 76.00 years STANDARD_DEVIATION 11.533 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) Score | 4.75 units on a scale STANDARD_DEVIATION 0.433 |
| Mini Mental Status Exam (MMSE) Score | 14.50 units on a scale STANDARD_DEVIATION 20.5061 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 3 |
| other Total, other adverse events | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Relationship of Flortaucipir Scan and Pathology - Cingulate Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of cingulate composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Cingulate Composite Region | 0.437 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: 0.12Spearman's Rank Order Correlation test
Primary
Relationship of Flortaucipir Scan and Pathology - Frontal Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of frontal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Frontal Composite Region | 0.681 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: <0.001Spearman's Rank Order Correlation test
Primary
Relationship of Flortaucipir Scan and Pathology - Limbic Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of limbic composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Limbic Composite Region | -0.189 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: 0.558Spearman's Rank Order Correlation test
Primary
Relationship of Flortaucipir Scan and Pathology - Occipital Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of occipital composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Occipital Composite Region | 0.564 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: 0.0958Spearman's Rank Order Correlation test
Primary
Relationship of Flortaucipir Scan and Pathology - Parietal Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of parietal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Parietal Composite Region | 0.644 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: 0.00278Spearman's Rank Order Correlation test
Primary
Relationship of Flortaucipir Scan and Pathology - Temporal Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of temporal composite region quantitation of the PET scan regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Temporal Composite Region | 0.324 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: 0.0712Spearman's Rank Order Correlation test
Primary
Relationship of Flortaucipir Scan and Pathology - Whole Cortical Composite Region
Correlation between flortaucipir standard uptake value ratio (SUVr) and neuropathology at autopsy. SUVr measurements for the analysis consisted of whole cortical global quantitation of the PET scan from 82 FreeSurfer-defined regions of interest (ROIs). Values were normalized to the brainstem to obtain the SUVr. Neuropathology was measured by immunohistology using AT8 antibody. Spearman correlation coefficient was calculated. Spearman correlation coefficients range from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation.
Time frame: autopsy within 6 months of scan
Population: One subject did not come to autopsy within 6 months of the flortaucipir scan.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Autopsy Cohort | Relationship of Flortaucipir Scan and Pathology - Whole Cortical Composite Region | 0.429 Correlation coefficient |
Comparison: Null hypothesis is no correlation (correlation coefficient = 0)p-value: <0.001Spearman's Rank Order Correlation test