Amyloid Beta-protein, Down Syndrome
Conditions
Keywords
Amyloid beta-protein, Down Syndrome
Brief summary
To determine the sensitivity of the visual assessment of BAY94-9172 PET images in detecting cerebral β-amyloid in individuals with Down Syndrome (DS) and specificity in individuals without DS. Given that individuals with Down Syndrome develop β-amyloid pathology over the age of 40, the clinical diagnosis of Down Syndrome will serve as the standard of truth.
Interventions
300 megabecquerels (MBq) as single IV injection of 2 to 10 mL
Sponsors
Life Molecular Imaging SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Study participants were individuals with DS and healthy volunteers (HVs). * Main inclusion criteria for individuals without DS * \>=21 and \<= 40 years of age * Mini-Mental State Examination (MMSE) \>= 28 * Clinical Dementia Rating (CDR) of 0 * Main inclusion criteria for individuals with DS * \>= 40 years of age
Exclusion criteria
* Main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome | 100-120 min | The primary variables are sensitivity (percentage of DS subjects positive for cerebral beta-amyloid) and specificity (percentage of healthy volunteers negative for cerebral beta-amyloid) of brain uptake of florbetaben based on the majority read of the visual assessment by three independent blinded readers of PET images obtained 100 to 120 minutes post-injection of florbetaben. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity Results in the Down Syndrome Age Subgroups | 100 - 120 min | The majority read sensitivity (percentage of DS subjects positive for cerebral beta-amyloid by majority read) was computed for the group of DS subjects with age equal to or below the median age (DS-young) and for DS subjects with age above the median age (DS-old). The median age was 46 yrs, with 3 subjects being exactly 46 yrs old. As defined, these subjects were assigned to the DS-young group. |
| Quantitative Parameters Standard Uptake Value Ratio | 100 - 120 min p.i. | The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, posterior cingulate, lateral temporal cortex, parietal cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference. |
| Consistency Between Visual and Quantitative Efficacy | 100 - 120 min | For a comparison of the results of the visual assessment with the quantitative assessment, descriptive Standardized Uptake Value Ratio (SUVR) statistics were computed separately for DS subjects with an abnormal/normal majority read of the PET scan (DS-PET+/DS-PET-). The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at two sites in the US.
Pre-assignment details
A total of 130 subjects were screened. 21 subjects were considered as screen failures and were not enrolled into the study. 9 subjects did not meet the inclusion/exclusion criteria. 10 subjects withdrew their consent. 1 subject was lost to follow-up and 1 subjected exceeded the weight limit for the camera.
Participants by arm
| Arm | Count |
|---|---|
| Subjects Enrolled in Study All Down Syndrome and healthy volunteer subjects | 109 |
| Total | 109 |
Baseline characteristics
| Characteristic | Subjects Enrolled in Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants |
| Age, Continuous Down Syndrome Group | 46.3 years STANDARD_DEVIATION 4.7 |
| Age, Continuous Healthy Volunteer Group | 27.7 years STANDARD_DEVIATION 5.1 |
| Region of Enrollment United States | 109 participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 39 | 5 / 70 |
| serious Total, serious adverse events | 0 / 39 | 0 / 70 |
Outcome results
Primary
Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome
The primary variables are sensitivity (percentage of DS subjects positive for cerebral beta-amyloid) and specificity (percentage of healthy volunteers negative for cerebral beta-amyloid) of brain uptake of florbetaben based on the majority read of the visual assessment by three independent blinded readers of PET images obtained 100 to 120 minutes post-injection of florbetaben.
Time frame: 100-120 min
Population: All subjects in the down syndrome population and healthy volunteers were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Majority Read | Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome | Sensitivity | 46.15 percentage of subjects |
| Majority Read | Sensitivity of the Independent Visual Assessment of Detecting Cerebral Amyloid-beta in Individuals With Down Syndrome and Specificity in Subjects Without Down Syndrome | Specificity | 100.00 percentage of subjects |
Secondary
Consistency Between Visual and Quantitative Efficacy
For a comparison of the results of the visual assessment with the quantitative assessment, descriptive Standardized Uptake Value Ratio (SUVR) statistics were computed separately for DS subjects with an abnormal/normal majority read of the PET scan (DS-PET+/DS-PET-). The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.
Time frame: 100 - 120 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Majority Read | Consistency Between Visual and Quantitative Efficacy | parietal cortex | 1.557 SUVR | Standard Deviation 0.2567 |
| Majority Read | Consistency Between Visual and Quantitative Efficacy | lateral temporal cortex | 1.498 SUVR | Standard Deviation 0.2396 |
| Majority Read | Consistency Between Visual and Quantitative Efficacy | frontal cortex | 1.566 SUVR | Standard Deviation 0.2372 |
| Majority Read | Consistency Between Visual and Quantitative Efficacy | posterior cingulate | 1.626 SUVR | Standard Deviation 0.2372 |
| Majority Read | Consistency Between Visual and Quantitative Efficacy | cerebellum, white matter | 1.698 SUVR | Standard Deviation 0.2396 |
| Majority Read (DS-Old) | Consistency Between Visual and Quantitative Efficacy | lateral temporal cortex | 1.223 SUVR | Standard Deviation 0.1092 |
| Majority Read (DS-Old) | Consistency Between Visual and Quantitative Efficacy | frontal cortex | 1.249 SUVR | Standard Deviation 0.1451 |
| Majority Read (DS-Old) | Consistency Between Visual and Quantitative Efficacy | posterior cingulate | 1.438 SUVR | Standard Deviation 0.2421 |
| Majority Read (DS-Old) | Consistency Between Visual and Quantitative Efficacy | parietal cortex | 1.250 SUVR | Standard Deviation 0.162 |
| Majority Read (DS-Old) | Consistency Between Visual and Quantitative Efficacy | cerebellum, white matter | 1.758 SUVR | Standard Deviation 0.1856 |
| Healthy Volunteer Group | Consistency Between Visual and Quantitative Efficacy | cerebellum, white matter | 1.769 SUVR | Standard Deviation 0.1302 |
| Healthy Volunteer Group | Consistency Between Visual and Quantitative Efficacy | parietal cortex | 1.138 SUVR | Standard Deviation 0.0742 |
| Healthy Volunteer Group | Consistency Between Visual and Quantitative Efficacy | frontal cortex | 1.146 SUVR | Standard Deviation 0.0749 |
| Healthy Volunteer Group | Consistency Between Visual and Quantitative Efficacy | lateral temporal cortex | 1.132 SUVR | Standard Deviation 0.0623 |
| Healthy Volunteer Group | Consistency Between Visual and Quantitative Efficacy | posterior cingulate | 1.329 SUVR | Standard Deviation 0.1118 |
Secondary
Quantitative Parameters Standard Uptake Value Ratio
The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, posterior cingulate, lateral temporal cortex, parietal cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.
Time frame: 100 - 120 min p.i.
Population: All Down Syndrome subjects and healthy volunteers enrolled in the study were included in this analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Majority Read | Quantitative Parameters Standard Uptake Value Ratio | posterior cingulate | 1.525 SUVR | Standard Deviation 0.2549 |
| Majority Read | Quantitative Parameters Standard Uptake Value Ratio | parietal cortex | 1.391 SUVR | Standard Deviation 0.2594 |
| Majority Read | Quantitative Parameters Standard Uptake Value Ratio | lateral temporal cortex | 1.350 SUVR | Standard Deviation 0.2265 |
| Majority Read | Quantitative Parameters Standard Uptake Value Ratio | cerebellum, white matter | 1.730 SUVR | Standard Deviation 0.2115 |
| Majority Read | Quantitative Parameters Standard Uptake Value Ratio | frontal cortex | 1.396 SUVR | Standard Deviation 0.2488 |
| Majority Read (DS-Old) | Quantitative Parameters Standard Uptake Value Ratio | cerebellum, white matter | 1.769 SUVR | Standard Deviation 0.1302 |
| Majority Read (DS-Old) | Quantitative Parameters Standard Uptake Value Ratio | frontal cortex | 1.146 SUVR | Standard Deviation 0.0749 |
| Majority Read (DS-Old) | Quantitative Parameters Standard Uptake Value Ratio | posterior cingulate | 1.329 SUVR | Standard Deviation 0.1118 |
| Majority Read (DS-Old) | Quantitative Parameters Standard Uptake Value Ratio | lateral temporal cortex | 1.132 SUVR | Standard Deviation 0.0623 |
| Majority Read (DS-Old) | Quantitative Parameters Standard Uptake Value Ratio | parietal cortex | 1.138 SUVR | Standard Deviation 0.0742 |
Secondary
Sensitivity Results in the Down Syndrome Age Subgroups
The majority read sensitivity (percentage of DS subjects positive for cerebral beta-amyloid by majority read) was computed for the group of DS subjects with age equal to or below the median age (DS-young) and for DS subjects with age above the median age (DS-old). The median age was 46 yrs, with 3 subjects being exactly 46 yrs old. As defined, these subjects were assigned to the DS-young group.
Time frame: 100 - 120 min
Population: All Down Syndrome subjects (n=39) were analyzed for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Majority Read | Sensitivity Results in the Down Syndrome Age Subgroups | 23.81 percentage of subjects |
| Majority Read (DS-Old) | Sensitivity Results in the Down Syndrome Age Subgroups | 72.22 percentage of subjects |