Brain Fibrillarab Levels
Conditions
Keywords
Amyloid, PET-Positron Emission Tomography, SUVR-Standard uptake value ratios
Brief summary
To determine the level of association between quantitative regional estimates of brain uptake of \[18F\]flutemetamol and quantitative immunohistochemical regional estimates of brain levels of amyloid estimated from post-mortem analysis of corresponding brain tissue samples.
Interventions
Flutemetamol (18F) Injection, 111 to 370 MBq (3 to 10 mCi), single intravenous injection.
Sponsors
i3 Statprobe
Covance
GE Healthcare
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject has a short life expectancy (approximately 1 year or less) as estimated by the Investigator. * The subject is 70 years of age or older if cognitively normal, or 55 years of age or older if terminal because of dementia. * The subject's general health is adequate to undergo the study procedures.
Exclusion criteria
* The subject has a contraindication for PET. * The subject has a known or suspected hypersensitivity/allergy to \[18F\]flutemetamol or to any of the excipients. * The subject is unable to tolerate or cooperate with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. | Post flutemetamol administration. | A calculation used to assess Sensitivity was (Number of Blinded Reads determined abnormal by Reader N) divided by the (Total number of abnormal participants). Blinded visual interpretations of \[18F\]flutemetamol Positron Emission Tomography (PET) images without anatomic brain images for detecting brain fibrillar amyloid β. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. | Post Flutemetamol administrations | A calculation used to assess Specificity was (Number of Blinded Reads determined normal by Reader N) divided by the (Total number of normal participants). Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as normal, without anatomic brain images. |
| Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. | Post flutemetamol administration. | Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as abnormal, with anatomic CT brain images for reference. |
| Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. | Post flutemetamol administration. | Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as normal, with anatomic CT brain images for reference. |
Countries
United States
Participant flow
Recruitment details
Study started on May, 2010 and ended on November 2011.
Pre-assignment details
23 subjects withdrew from study prior to dosing of the product.
Participants by arm
| Arm | Count |
|---|---|
| Flutemetamol Injection \[18F\]flutemetamol (less than 10 microgram (ug) flutemetamol). The nominal activity of a single administration of \[18F\]flutemetamol was 185 to 370 megabecquerels (MBq). | 180 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 23 |
Baseline characteristics
| Characteristic | Flutemetamol Injection |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 165 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age Continuous | 79.9 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment United Kingdom | 12 participants |
| Region of Enrollment United States | 168 participants |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 180 |
| serious Total, serious adverse events | 4 / 180 |
Outcome results
Primary
The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β.
A calculation used to assess Sensitivity was (Number of Blinded Reads determined abnormal by Reader N) divided by the (Total number of abnormal participants). Blinded visual interpretations of \[18F\]flutemetamol Positron Emission Tomography (PET) images without anatomic brain images for detecting brain fibrillar amyloid β.
Time frame: Post flutemetamol administration.
Population: The assessments were post-mortum based on the estimates of the presence of amyloid plaque in the brain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity Percentage of Abnormal Visual Reads | The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. | Reader 1- Abnormal | 81 Percentage of Sensitivity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. | Reader 2 - Abnormal | 88 Percentage of Sensitivity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. | Reader 3 - Abnormal | 93 Percentage of Sensitivity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. | Reader 4 - Abnormal | 93 Percentage of Sensitivity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. | Reader 5 - Abnormal | 88 Percentage of Sensitivity by Reader |
Secondary
Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference.
Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as abnormal, with anatomic CT brain images for reference.
Time frame: Post flutemetamol administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. | Reader 1 | 91 Percent of Sensitivity-Abnormal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. | Reader 2 | 95 Percent of Sensitivity-Abnormal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. | Reader 3 | 98 Percent of Sensitivity-Abnormal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. | Reader 4 | 91 Percent of Sensitivity-Abnormal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. | Reader 5 | 91 Percent of Sensitivity-Abnormal Reads |
Secondary
Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference.
Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as normal, with anatomic CT brain images for reference.
Time frame: Post flutemetamol administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. | Reader 1 | 92 Percent of Specificity-Normal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. | Reader 2 | 88 Percent of Specificity-Normal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. | Reader 3 | 56 Percent of Specificity-Normal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. | Reader 4 | 88 Percent of Specificity-Normal Reads |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. | Reader 5 | 92 Percent of Specificity-Normal Reads |
Secondary
Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images.
A calculation used to assess Specificity was (Number of Blinded Reads determined normal by Reader N) divided by the (Total number of normal participants). Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as normal, without anatomic brain images.
Time frame: Post Flutemetamol administrations
Population: The assessment was done post-mortum based on the estimates of the presence of amyloid plaque in the brain.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. | Reader 1 - Normal | 88 Percentage of Specificity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. | Reader 2 - Normal | 92 Percentage of Specificity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. | Reader 3 - Normal | 44 Percentage of Specificity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. | Reader 4 - Normal | 80 Percentage of Specificity by Reader |
| Sensitivity Percentage of Abnormal Visual Reads | Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. | Reader 5 - Normal | 92 Percentage of Specificity by Reader |