Alzheimer's Disease
Conditions
Brief summary
This study is designed to demonstrate the conversion of florbetapir (18F) Positron Emission Tomography (PET) Standard Uptake Value ratio (SUVr) to Centiloid units.
Interventions
DRUG11C-PiB
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Cognitively Normal Subjects * Males or females ≥ 21 and ≤ 45 years of age * Mini-mental state examination (MMSE) ≥ 29 * Clinically Diagnosed AD Subject * Males or females ≥ 50 years of age * Meet clinical criteria for dementia due to probable AD * MMSE ≥ 16 and ≤ 26 * Possible AD Subject * Males or females ≥ 50 years of age * Meet clinical criteria for dementia due to possible AD * MMSE ≥ 16 and ≤ 26 * MCI Subject * Males or females ≥ 60 years of age with cognitive impairment (not dementia) * MMSE \>24 and \<29 * At Risk Elderly Subject * Cognitively normal males or females that are known ApoE4 carriers and ≥ 75 years of age * MMSE ≥ 27
Exclusion criteria
* Have had or currently have a diagnosis of neurodegenerative disorders other than AD * Have a current serious or unstable illness that could interfere with completion of the study * Subject has a known brain lesion, pathology or traumatic brain injury * Have received or participated in a trial with investigational medications in the past 30 days * Have had a radiopharmaceutical imaging or treatment procedure within 7 days of study imaging session * Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Florbetapir SUVr Conversion to Centiloid Units | up to 70 minutes post injection | Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (\<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | up to 70 minutes post injection | Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (\<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure. |
| Variability of PET Images in Young Healthy Control Subjects. | up to 70 minutes post injection | Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure. |
Countries
Australia, United States
Participant flow
Recruitment details
First subject enrolled: 14 April 2014; Last subject completed: 18 September 2015
Participants by arm
| Arm | Count |
|---|---|
| Clincally Diagnosed AD Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) | 10 |
| Possible AD Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease | 4 |
| Mild Cognitive Impairment (MCI) Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater | 7 |
| At Risk Elderly Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal | 4 |
| Young Healthy Controls (YHC) Cognitively normal young subjects between 21 and 45 years of age (inclusive) | 10 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Clincally Diagnosed AD | Possible AD | Mild Cognitive Impairment (MCI) | At Risk Elderly | Young Healthy Controls (YHC) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 69.2 years STANDARD_DEVIATION 4.94 | 66 years STANDARD_DEVIATION 4.76 | 79.9 years STANDARD_DEVIATION 8.47 | 79.3 years STANDARD_DEVIATION 2.5 | 27.3 years STANDARD_DEVIATION 4.83 | 60.1 years STANDARD_DEVIATION 22.28 |
| Mini Mental Status Exam | 23.7 units on a scale STANDARD_DEVIATION 2.45 | 21.8 units on a scale STANDARD_DEVIATION 4.92 | 26.4 units on a scale STANDARD_DEVIATION 1.27 | 29.3 units on a scale STANDARD_DEVIATION 0.96 | 29.5 units on a scale STANDARD_DEVIATION 0.53 | 26.3 units on a scale STANDARD_DEVIATION 3.55 |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 6 Participants | 4 Participants | 3 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 35 | 0 / 34 | 0 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 35 | 0 / 34 | 0 / 34 |
Outcome results
Primary
Florbetapir SUVr Conversion to Centiloid Units
Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (\<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
Time frame: up to 70 minutes post injection
Population: All participants receiving both a florbetapir and a PiB scan per protocol. One subject in the possible AD group did not complete a florbetapir scan due to excessive movement. One subject in the at risk elderly group elected to leave the study before the second PET scan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clincally Diagnosed AD | Florbetapir SUVr Conversion to Centiloid Units | 82.44 centiloid | Standard Deviation 45.623 |
| Possible AD | Florbetapir SUVr Conversion to Centiloid Units | 50.75 centiloid | Standard Deviation 60.383 |
| Mild Cognitive Impairment (MCI) | Florbetapir SUVr Conversion to Centiloid Units | 81.19 centiloid | Standard Deviation 66.357 |
| At Risk Elderly | Florbetapir SUVr Conversion to Centiloid Units | 14.93 centiloid | Standard Deviation 35.885 |
| Young Healthy Controls (YHC) | Florbetapir SUVr Conversion to Centiloid Units | 5.24 centiloid | Standard Deviation 11.981 |
Secondary
Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid
Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (\<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
Time frame: up to 70 minutes post injection
Population: All participants receiving both a florbetapir and a PiB scan per protocol. One subject in the possible AD group did not complete the florbetapir scan due to excessive movement. One subject in the at risk elderly group elected to leave the study before the second PET scan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clincally Diagnosed AD | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | Florbetapir | 82.44 centiloid | Standard Deviation 45.623 |
| Clincally Diagnosed AD | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | 11C-PiB | 87.18 centiloid | Standard Deviation 41.105 |
| Possible AD | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | Florbetapir | 50.75 centiloid | Standard Deviation 60.383 |
| Possible AD | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | 11C-PiB | 54.52 centiloid | Standard Deviation 56.511 |
| Mild Cognitive Impairment (MCI) | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | Florbetapir | 81.19 centiloid | Standard Deviation 66.357 |
| Mild Cognitive Impairment (MCI) | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | 11C-PiB | 74.33 centiloid | Standard Deviation 57.597 |
| At Risk Elderly | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | 11C-PiB | 26.39 centiloid | Standard Deviation 37.464 |
| At Risk Elderly | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | Florbetapir | 14.93 centiloid | Standard Deviation 35.885 |
| Young Healthy Controls (YHC) | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | Florbetapir | 5.24 centiloid | Standard Deviation 11.981 |
| Young Healthy Controls (YHC) | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid | 11C-PiB | 0.73 centiloid | Standard Deviation 2.414 |
Regression, Linear
Secondary
Variability of PET Images in Young Healthy Control Subjects.
Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure.
Time frame: up to 70 minutes post injection
Population: Young healthy controls enrolled in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clincally Diagnosed AD | Variability of PET Images in Young Healthy Control Subjects. | 1.01 SUVr | Standard Deviation 0.026 |
| Possible AD | Variability of PET Images in Young Healthy Control Subjects. | 0.98 SUVr | Standard Deviation 0.066 |