Alzheimer's Disease
Conditions
Keywords
Amyloid imaging, Positron Emission Tomography, 18F-AV-45, florbetapir F 18, Diagnostic imaging
Brief summary
The purpose of this study is re-read of brain amyloid positron emission tomography (PET) scans acquired in previous florbetapir F 18 clinical studies by readers trained using updated reading methodology. The scans in this study came from subjects who had an autopsy to reveal the subject's true amyloid status.
Interventions
DRUGflorbetapir F 18
IV injection, 370MBq (10mCi), single dose
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Study A07\[NCT00857415\]): * Have a projected life expectancy of ≤ 6 months as determined by the principal investigator (e.g. terminal medical condition) or are already enrolled in a longitudinal study of aging with an autopsy component; * Can tolerate a 10 minute PET scan; and * Give informed consent for 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.
Exclusion criteria
(Study A07\[NCT00857415\]): * Have primary brain tumor, known metastases to the brain, central nervous system (CNS) lymphoma; * Have any major, focal structural loss of brain matter; * Are aggressively being treated with life sustaining measures (e.g. currently on respirator; receiving high dose chemotherapy); * Have a clinically significant infectious disease, including Acquired Immune Deficiency Syndrome (AIDS), Human Immunodeficiency Virus (HIV) infection, previous positive test for hepatitis or HIV or Creutzfeldt-Jakob disease (CJD); * Are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days; * Have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, secretase inhibitor); * Have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session; or * Are females of childbearing potential who are pregnant or not using adequate contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of Florbetapir PET Scans to Detect Moderate to Frequent Amyloid Plaque | 50-60 min after injection | Nine readers blinded to all clinical information using the binary read methodology (amyloid positive/negative). Sensitivity will be calculated as the percent of true positives (as determined by the reference standard, moderate or frequent amyloid plaque at autopsy) that are correctly identified as amyloid positive by the PET scan read. Reported as the median sensitivity of the nine readers. |
| Specificity of Florbetapir PET Scans to Detect Moderate to Frequent Amyloid Plaque | 50-60 min after injection | Nine readers blinded to all clinical information using the binary read methodology (amyloid positive/negative). Specificity will be calculated as the percent of true negatives (as determined by the reference standard, no or sparse amyloid plaque at autopsy) that are correctly identified as amyloid negative by the PET scan read. Reported as the median specificity of the nine readers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inter-reader Agreement | 50-60 min after injection | Percentage of individual scan reads that agreed or disagreed with the majority read across nine readers |
Participant flow
Recruitment details
NO SUBJECTS WERE ENROLLED IN THIS STUDY - this study re-read scans obtained in other clinical studies
Participants by arm
| Arm | Count |
|---|---|
| All A07 Autopsy Subjects Subjects who had a valid florbetapir-PET scan and came to autopsy in Study A07 | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | All A07 Autopsy Subjects |
|---|---|
| Age Continuous | 79.3 years STANDARD_DEVIATION 13.3 |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Sensitivity of Florbetapir PET Scans to Detect Moderate to Frequent Amyloid Plaque
Nine readers blinded to all clinical information using the binary read methodology (amyloid positive/negative). Sensitivity will be calculated as the percent of true positives (as determined by the reference standard, moderate or frequent amyloid plaque at autopsy) that are correctly identified as amyloid positive by the PET scan read. Reported as the median sensitivity of the nine readers.
Time frame: 50-60 min after injection
Population: 19 of the 35 subjects had moderate or frequent plaques at autopsy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All A07(NCT00857415) Autopsy Subjects | Sensitivity of Florbetapir PET Scans to Detect Moderate to Frequent Amyloid Plaque | 100 percentage of true positives |
Primary
Specificity of Florbetapir PET Scans to Detect Moderate to Frequent Amyloid Plaque
Nine readers blinded to all clinical information using the binary read methodology (amyloid positive/negative). Specificity will be calculated as the percent of true negatives (as determined by the reference standard, no or sparse amyloid plaque at autopsy) that are correctly identified as amyloid negative by the PET scan read. Reported as the median specificity of the nine readers.
Time frame: 50-60 min after injection
Population: 16 of the 35 subjects had none or sparse plaques at autopsy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All A07(NCT00857415) Autopsy Subjects | Specificity of Florbetapir PET Scans to Detect Moderate to Frequent Amyloid Plaque | 93.8 percentage of true negatives |
Secondary
Inter-reader Agreement
Percentage of individual scan reads that agreed or disagreed with the majority read across nine readers
Time frame: 50-60 min after injection
Population: 315 scans = 35 subjects x 9 readers
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All A07(NCT00857415) Autopsy Subjects | Inter-reader Agreement | Agreed with majority read | 96.2 percentage of scans |
| All A07(NCT00857415) Autopsy Subjects | Inter-reader Agreement | Discrepant with majority read | 3.8 percentage of scans |
Comparison: Fleiss' kappap-value: <0.0001Fleiss' kappa